MicroRNAs(miRNAs)have received much attention in the past decade as potential key epigenomic regulators of tumors and cancer stem cells(CSCs).The abnormal expression of miRNAs is responsible for different phenotypes o...MicroRNAs(miRNAs)have received much attention in the past decade as potential key epigenomic regulators of tumors and cancer stem cells(CSCs).The abnormal expression of miRNAs is responsible for different phenotypes of gastric cancer stem cells(GCSCs).Some specific miRNAs could be used as promising biomarkers and therapeutic targets for the identification of GCSCs.This review summarizes the coding process and biological functions of miRNAs and demon-strates their role and efficacy in gastric cancer(GC)metastasis,drug resistance,and apoptosis,especially in the regulatory mechanism of GCSCs.It shows that the overexpression of onco-miRNAs and silencing of tumor-suppressor miRNAs can play a role in promoting or inhibiting tumor metastasis,apart from the initial formation of GC.It also discusses the epigenetic regulation and potential clinical applications of miRNAs as well as the role of CSCs in the pathogenesis of GC.We believe that this review may help in designing novel therapeutic approaches for GC.展开更多
Objective:To explore the effect and mechanism of prostaglandins D2(PGD2)on the stemness of gastric cancer stem cells(GCSCs).Methods:7901-GCSCs were enriched by serum-free culture method;then the positivity rate of CD4...Objective:To explore the effect and mechanism of prostaglandins D2(PGD2)on the stemness of gastric cancer stem cells(GCSCs).Methods:7901-GCSCs were enriched by serum-free culture method;then the positivity rate of CD44,a stemness marker,was detected by flow cytometry in serum-free cultured 7901-GCSCs;the sphere-forming ability was detected by the sphere-forming assay after stimulation with different concentrations of PGD2(2.5,5,10)μg/mL,and the expression of stemness-related indicators(OCT4,CD44)and autophagyrelated proteins(LC3,Beclin-1)after PGD2 stimulation was detected by the western blot assay in different concentrations.The expression of stemness-related indexes(OCT4,CD44)and autophagy-related proteins(LC3,Beclin-1)were detected by Western blot assay after stimulation with different concentrations of PGD2.The expression of autophagy-related proteins after stimulation with different concentrations of CQ(2.5,5,10)μM was detected by Western blot experiment.The protein expression of autophagy-related proteins(LC3,Beclin-1)and stemness-related indexes(OCT4,CD44)was detected by Western blot experiment after PGD2 as well as PGD2+CQ treatment.Results:Flow cytometry results showed that the expression of CD44 positivity was increased in serum-free cultured 7901-GCSCs compared with gastric cancer cells SGC-7901(P<0.05),which fulfilled the needs of subsequent experiments.The results of stem cell spheroid formation assay showed that the spheroid formation ability of 7901-GCSCs in the PGD2 group was significantly weakened compared with that of the DMSO group(P<0.05).Western blot results showed that the protein expression of stemness-related indexes(OCT4,CD44)was down-regulated in the 7901-GCSCs in the PGD2 group compared with that of the DMSO group(P<0.05),and the expression of autophagy-related proteins(LC3,Beclin-1)expression increased(P<0.05).Compared with the DMSO group,the expression of autophagy-related proteins(LC3,Beclin-1)was decreased in the CQ group(P<0.05).Western blot results also showed that the expression of cellular autophagy-related proteins and stemness-related indexes in the PGD2+CQ group was not significantly changed compared with that of the DMSO group(ns:the difference was not significant),suggesting that the CQ could block the effect of PGD2 on the expression of stemness markers in 7901-GCSCs.7901-GCSCs stemness inhibition.Conclusion:PGD2 may affect the stemness of 7901-GCSCs by regulating autophagy.展开更多
Lung cancer is the leading cause of cancer-related deaths globally.In recent years,with the widespread use of genetic testing,epidermal growth factor receptor–tyrosine kinase inhibitor(EGFR-TKI)–targeted drugs have ...Lung cancer is the leading cause of cancer-related deaths globally.In recent years,with the widespread use of genetic testing,epidermal growth factor receptor–tyrosine kinase inhibitor(EGFR-TKI)–targeted drugs have been efficacious to patients with lung adenocarcinoma exhibiting EGFR mutations.However,resistance to treatment is inevitable and eventually leads to tumor progression,recurrence,and reduction in the overall treatment efficacy.Lung cancer stem cells play a crucial role in the development of resistance toward EGFR-TKI–targeted therapy for lung adenocarcinoma.Lung cancer stem cells possess self-renewal,multilineage differentiation,and unlimited proliferation capabilities,which efficiently contribute to tumor formation and ultimately lead to tumor recurrence andmetastasis.In this study,we evaluated the origin,markers,stemness index,relevant classic studies,resistance mechanisms,related signaling pathways,and strategies for reversing lung cancer stem cell resistance to EGFR-TKIs to provide new insights on delaying or reducing resistance and to improve the treatment efficacy of patients with EGFR-mutated lung adenocarcinoma in the future.展开更多
Prostate cancer, one of the most frequently occurring cancers in men, is a heterogeneous disease involving multiple cell types within tumors. This tumor heterogeneity at least partly results from genomic instability l...Prostate cancer, one of the most frequently occurring cancers in men, is a heterogeneous disease involving multiple cell types within tumors. This tumor heterogeneity at least partly results from genomic instability leading to sub-clonal cellular differentiation. The differentiated cell populations originate from a small subset of cells with tumor-initiating and stem-like properties. These cells, termed prostate cancer stem cells(PCSCs), play crucial roles in disease progression, drug resistance, and relapse. This review discusses the origin, hierarchy, and plasticity of PCSCs;methods for isolation and enrichment of PCSCs;and various cellular and metabolic signaling pathways involved in PCSC induction and maintenance, as well as therapeutic targeting.展开更多
Cancer stem cells(CSCs) are a small subset of cells in cancers that are thought to initiate tumorous transformation and promote metastasis, recurrence, and resistance to treatment. Growing evidence has revealed the ex...Cancer stem cells(CSCs) are a small subset of cells in cancers that are thought to initiate tumorous transformation and promote metastasis, recurrence, and resistance to treatment. Growing evidence has revealed the existence of CSCs in various types of cancers and suggested that CSCs differentiate into diverse lineage cells that contribute to tumor progression. We may be able to overcome the limitations of cancer treatment with a comprehensive understanding of the biological features and mechanisms underlying therapeutic resistance in CSCs. This review provides an overview of the properties, biomarkers, and mechanisms of resistance shown by CSCs. Recent findings on metabolic features, especially fatty acid metabolism and ferroptosis in CSCs, are highlighted, along with promising targeting strategies. Targeting CSCs is a potential treatment plan to conquer cancer and prevent resistance and relapse in cancer treatment.展开更多
Over the past 2 decades,cancer stem cells(CSCs)have been identified as the root cause of cancer occurrence,progression,chemoradioresistance,recurrence,and metastasis.Targeting CSCs is a novel therapeutic strategy for ...Over the past 2 decades,cancer stem cells(CSCs)have been identified as the root cause of cancer occurrence,progression,chemoradioresistance,recurrence,and metastasis.Targeting CSCs is a novel therapeutic strategy for cancer management and treatment.Liver cancer(LC)is a malignant disease that can endanger human health.Studies are increasingly suggesting that changes in the liver mechanical microenvironment are a primary driver triggering the occurrence and development of liver cancer.In this review,we summarize current understanding of the roles of the liver mechano-microenvironment and liver cancer stem cells(LCSCs)in liver cancer progression.We also discuss the relationship between the mechanical heterogeneity of liver cancer tissues and LCSC recruitment and metastasis.Finally,we highlight potential mechanosensitive molecules in LCSCs and mechanotherapy in liver cancer.Understanding the roles and regulatory mechanisms of the mechano-microenvironment and LCSCs may provide fundamental insights into liver cancer progression and aid in further development of novel therapeutic strategies.展开更多
Cancer stem cells(CSCs)are a small proportion of the cells that exist in cancer tissues.They are considered to be the culprit of tumor genesis,development,drug resistance,metastasis and recurrence because of their sel...Cancer stem cells(CSCs)are a small proportion of the cells that exist in cancer tissues.They are considered to be the culprit of tumor genesis,development,drug resistance,metastasis and recurrence because of their self-renewal,proliferation,and differentiation potential.The elimination of CSCs is thus the key to cure cancer,and targeting CSCs provides a new method for tumor treatment.Due to the advantages of controlled sustained release,targeting and high biocompatibility,a variety of nanomaterials are used in the diagnosis and treatments targeting CSCs and promote the recognition and removal of tumor cells and CSCs.This article mainly reviews the research progress of nanotechnology in sorting CSCs and nanodrug delivery systems targeting CSCs.Furthermore,we identify the problems and future research directions of nanotechnology in CSC therapy.We hope that this review will provide guidance for the design of nanotechnology as a drug carrier so that it can be used in clinic for cancer therapy as soon as possible.展开更多
Cancer stem cells(CSCs)are the main cause of tumor growth,invasion,metastasis and recurrence.Recently,CSCs have been extensively studied to identify CSCspecific surface markers as well as signaling pathways that play ...Cancer stem cells(CSCs)are the main cause of tumor growth,invasion,metastasis and recurrence.Recently,CSCs have been extensively studied to identify CSCspecific surface markers as well as signaling pathways that play key roles in CSCs self-renewal.The involvement of CSCs in the pathogenesis of gastrointestinal(GI)cancers also highlights these cells as a priority target for therapy.The diagnosis,prognosis and treatment of GI cancer have always been a focus of attention.Therefore,the potential application of CSCs in GI cancers is receiving increasing attention.This review summarizes the role of CSCs in GI cancers,focusing on esophageal cancer,gastric cancer,liver cancer,colorectal cancer,and pancreatic cancer.In addition,we propose CSCs as potential targets and therapeutic strategies for the effective treatment of GI cancers,which may provide better guidance for clinical treatment of GI cancers.展开更多
Obesity,the global pandemic since industrialization,is the number one lifestylerelated risk factor for premature death,which increases the incidence and mortality of various diseases and conditions,including cancer.In...Obesity,the global pandemic since industrialization,is the number one lifestylerelated risk factor for premature death,which increases the incidence and mortality of various diseases and conditions,including cancer.In recent years,the theory of cancer stem cells(CSCs),which have the capacity for self-renewal,metastasis and treatment resistance,has been bolstered by increasing evidence.However,research on how obesity affects CSCs to facilitate cancer initiation,progression and therapy resistance is still in its infancy,although evidence has already begun to accumulate.Regarding the ever-increasing burden of obesity and obesity-related cancer,it is pertinent to summarize evidence about the effects of obesity on CSCs,as elucidating these effects will contribute to the improvement in the management of obesity-related cancers.In this review,we discuss the association between obesity and CSCs,with a particular focus on how obesity promotes cancer initiation,progression and therapy resistance through CSCs and the mechanisms underlying these effects.In addition,the prospect of preventing cancer and targeting the mechanisms linking obesity and CSCs to reduce cancer risk or to improve the survival of patients with cancer is considered.展开更多
Head and neck squamous cell carcinoma is the seventh most common cancer worldwide with high mortality rates.Amongst oral cavity cancers,tongue carcinoma is a very common and aggressive oral cavity carcinoma.Despite th...Head and neck squamous cell carcinoma is the seventh most common cancer worldwide with high mortality rates.Amongst oral cavity cancers,tongue carcinoma is a very common and aggressive oral cavity carcinoma.Despite the implementation of a multimodality treatment regime including surgical intervention,chemo-radiation as well as targeted therapy,tongue carcinoma shows a poor overall 5-year survival pattern,which is attributed to therapy resistance and recurrence of the disease.The presence of a rare population,i.e.,cancer stem cells(CSCs)within the tumor,are involved in therapy resistance,recurrence,and distant metastasis that results in poor survival patterns.Therapeutic agents targeting CSCs have been in clinical trials,although they are unable to reach into therapy stage which is due to their failure in trials.A more detailed understanding of the CSCs is essential for identifying efficient targets.Molecular signaling pathways,which are differentially regulated in the CSCs,are one of the promising targets to manipulate the CSCs that would provide an improved outcome.In this review,we summarize the current understanding of molecular signaling associated with the maintenance and regulation of CSCs in tongue squamous cell carcinoma in order to emphasize the need of the hour to get a deeper understanding to unravel novel targets.展开更多
Objective:To evaluate the effects of ethanol extract from Ardisia gigantifolia leaves on cell proliferation and cancer stem cell(CSC)number in gastric cancer.Methods:The inhibitory effect of Ardisia gigantifolia extra...Objective:To evaluate the effects of ethanol extract from Ardisia gigantifolia leaves on cell proliferation and cancer stem cell(CSC)number in gastric cancer.Methods:The inhibitory effect of Ardisia gigantifolia extract on the proliferation of MKN45 and MKN74 gastric cancer cells was assessed using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay.Non-adherent culture(3D)model was used to evaluate the effect of the extract on tumorsphere size and number.Moreover,the expression of CD44,ALDH,and p21 was determined by immunofluorescence analysis.Flow cytometric analysis was performed to evaluate cell cycle arrest and the expression of gastric CSC markers CD44 and ALDH.Real-time PCR analysis was also carried out to assess the effect of the extract on the expression of cell cycle-regulated genes.Results:Ardisia gigantifolia extract effectively inhibited cell proliferation with an IC_(50)of 55.7μg/m L in MKN45 cells and 123.6μg/m L in MKN74 cells.The extract also arrested cell cycle in the G_(0)/G_(1)phase as well as significantly reduced the size and number of tumorspheres.The markedly increased expression of p21 was observed at both m RNA and protein levels in the extract-treated adherent cells and tumorspheres.In addition,Ardisia gigantifolia extract significantly reduced the number of CD44-and/or ALDH-expressing gastric CSC.Conclusions:The development of gastric CSC can be inhibited by the ethanol extract of Ardisia gigantifolia.展开更多
Cancer stem cells(CSCs)are tumor cells that share functional characteristics with normal and embryonic stem cells.CSCs have increased tumor-initiating capacity and metastatic potential and lower sensitivity to chemo-a...Cancer stem cells(CSCs)are tumor cells that share functional characteristics with normal and embryonic stem cells.CSCs have increased tumor-initiating capacity and metastatic potential and lower sensitivity to chemo-and radiotherapy,with important roles in tumor progression and the response to therapy.Thus,a current goal of cancer research is to eliminate CSCs,necessitating an adequate phenotypic and functional characterization of CSCs.Strategies have been developed to identify,enrich,and track CSCs,many of which distinguish CSCs by evaluating the expression of surface markers,the initiation of specific signaling pathways,and the activation of master transcription factors that control stemness in normal cells.We review and discuss the use of reporter gene systems for identifying CSCs.Reporters that are under the control of aldehyde dehydrogenase 1A1,CD133,Notch,Nanog homeobox,Sex-determining region Y-box 2,and POU class 5 homeobox can be used to identify CSCs in many tumor types,track cells in real time,and screen for drugs.Thus,reporter gene systems,in combination with in vitro and in vivo functional assays,can assess changes in the CSCs pool.We present relevant examples of these systems in the evaluation of experimental CSCs-targeting therapeutics,demonstrating their value in CSCs research.展开更多
The cancer stem cells(CSCs)from human osteosarcoma by serum-free three-dimensional culture combined with anticancer drugs were isolated and identified.The primary cells derived from human osteosarcoma were digested by...The cancer stem cells(CSCs)from human osteosarcoma by serum-free three-dimensional culture combined with anticancer drugs were isolated and identified.The primary cells derived from human osteosarcoma were digested by trypsin to prepare a single-cell suspension,and mixed homogeneously into 1.2% alginate gel.Single-cell alginate gel was cultured with serum-free DMEM/F12 medium.Epirubicin(0.8μg/mL)was added to the medium to enrich CSCs.After cultured conventionally for 7 to 10 days,most of cells suspended in alginate gel were killed by epirubicin.But few cells survived and some single-cell cloning spheres formed.Immunofluorescent staining for Oct3/4 and Nanog was implemented to find cells with properties of self-renewal and multi-potential differentiation.Cells from cloning spheres were transplanted into BALB/c mice to detect the tumorigenicity in vivo.The results showed that some cells positive for Oct3/4(TRITC)and Nanog(TRITC)were found in single-cell cloning spheres,and most of positive cells were concentrated in the core of sphere.Cells from spheres could form osteosarcoma in the body of mice.It was concluded that cells from single-cell cloning spheres had the properties of the expression of parts of stem cell genes(Oct3/4 and Nanog),resisting anti-cancer drugs,and tumorigenicity in vivo.To sum up,it is believed that cells obtained from osteosarcoma by serum-free three-dimensional culture combined with anticancer drugs are cancer stem cells.展开更多
Gastrointestinal cancer has been one of the five most commonly diagnosed and leading causes of cancer mortality over the past few decades. Great progress in traditional therapies has been made, which prolonged surviva...Gastrointestinal cancer has been one of the five most commonly diagnosed and leading causes of cancer mortality over the past few decades. Great progress in traditional therapies has been made, which prolonged survival in patients with early cancer, yet tumor relapse and drug resistance still occurred, which is explained by the cancer stem cell(CSC) theory. Oncolytic virotherapy has attracted increasing interest in cancer because of its ability to infect and lyse CSCs. This paper reviews the basic knowledge, CSC markers and therapeutics of gastrointestinal cancer(liver, gastric, colon and pancreatic cancer), as well as research advances and possible molecular mechanisms of various oncolytic viruses against gastrointestinal CSCs. This paper also summarizes the existing obstacles to oncolytic virotherapy and proposes several alternative suggestions to overcome the therapeutic limitations.展开更多
Epigenetic modifications have been observed as a decline in miRNA-21 expression and breast cancer stem cell(CSC)population after 3 cycles of standard chemotherapy.The epigenetic response(miRNAs expression)and CSCs are...Epigenetic modifications have been observed as a decline in miRNA-21 expression and breast cancer stem cell(CSC)population after 3 cycles of standard chemotherapy.The epigenetic response(miRNAs expression)and CSCs are also correlated in patients with Breast Cancer.In patients who tolerated chemotherapy well,miRNA-21(non-coding RNA)expression decreased significantly after three cycles of chemotherapy.The miRNA-21 expression in breast cancer tissue was quantified by quantitative PCR(real-time PCR)using the standard protocol.In addition,breast CSCs(CD44+/CD24-)were also decreased in these patients.The miRNA-21 regulates cell division,proliferation,and autophagy of cancerous cells(as it targets phosphatase and tensin homolog/AKT/transcription factor EB/programmed cell death 4/autophagy-related protein 5 and chemotherapy also produces similar effects),thereby contributing to these benefits.Therefore,when all of the targets on genes have been explored by mimic miRNA,chemotherapy combined with anti-miRNA21 therapy may prove useful in the care of cancer patients.展开更多
Autophagy is a highly regulated catabolic process in which superfluous,damaged organelles and other cytoplasmic constituents are delivered to the lysosome for clearance and the generation of macromolecule substrates d...Autophagy is a highly regulated catabolic process in which superfluous,damaged organelles and other cytoplasmic constituents are delivered to the lysosome for clearance and the generation of macromolecule substrates during basal or stressed conditions.Autophagy is a bimodal process with a context dependent role in the initiation and the development of cancers.For instance,autophagy provides an adaptive response to cancer stem cells to survive metabolic stresses,by influencing disease propagation via modulation of essential signaling pathways or by promoting resistance to chemotherapeutics.Autophagy has been implicated in a cross talk with apoptosis.Understanding the complex interactions provides an opportunity to improve cancer therapy and the clinical outcome for the cancer patients.In this review,we provide a comprehensive view on the current knowledge on autophagy and its role in cancer cells with a particular focus on cancer stem cell homeostasis.展开更多
BACKGROUND Cellular metabolism regulates stemness in health and disease.A reduced redox state is essential for self-renewal of normal and cancer stem cells(CSCs).However,while stem cells rely on glycolysis,different C...BACKGROUND Cellular metabolism regulates stemness in health and disease.A reduced redox state is essential for self-renewal of normal and cancer stem cells(CSCs).However,while stem cells rely on glycolysis,different CSCs,including pancreatic CSCs,favor mitochondrial metabolism as their dominant energy-producing pathway.This suggests that powerful antioxidant networks must be in place to detoxify mitochondrial reactive oxygen species(ROS)and maintain stemness in oxidative CSCs.Since glutathione metabolism is critical for normal stem cell function and CSCs from breast,liver and gastric cancer show increased glutathione content,we hypothesized that pancreatic CSCs also rely on this pathway for ROS detoxification.AIM To investigate the role of glutathione metabolism in pancreatic CSCs.METHODS Primary pancreatic cancer cells of patient-derived xenografts(PDXs)were cultured in adherent or CSC-enriching sphere conditions to determine the role of glutathione metabolism in stemness.Real-time polymerase chain reaction(PCR)was used to validate RNAseq results involving glutathione metabolism genes in adherent vs spheres,as well as the expression of pluripotency-related genes following treatment.Public TCGA and GTEx RNAseq data from pancreatic cancer vs normal tissue samples were analyzed using the webserver GEPIA2.The glutathione-sensitive fluorescent probe monochlorobimane was used to determine glutathione content by fluorimetry or flow cytometry.Pharmacological inhibitors of glutathione synthesis and recycling[buthionine-sulfoximine(BSO)and 6-Aminonicotinamide(6-AN),respectively]were used to investigate the impact of glutathione depletion on CSC-enriched cultures.Staining with propidium iodide(cell cycle),Annexin-V(apoptosis)and CD133(CSC content)were determined by flow cytometry.Self-renewal was assessed by sphere formation assay and response to gemcitabine treatment was used as a readout for chemoresistance.RESULTS Analysis of our previously published RNAseq dataset E-MTAB-3808 revealed upregulation of genes involved in the KEGG(Kyoto Encyclopedia of Genes and Genomes)Pathway Glutathione Metabolism in CSC-enriched cultures compared to their differentiated counterparts.Consistently,in pancreatic cancer patient samples the expression of most of these up-regulated genes positively correlated with a stemness signature defined by NANOG,KLF4,SOX2 and OCT4 expression(P<10-5).Moreover,3 of the upregulated genes(MGST1,GPX8,GCCT)were associated with reduced disease-free survival in patients[Hazard ratio(HR)2.2-2.5;P=0.03-0.0054],suggesting a critical role for this pathway in pancreatic cancer progression.CSC-enriched sphere cultures also showed increased expression of different glutathione metabolism-related genes,as well as enhanced glutathione content in its reduced form(GSH).Glutathione depletion with BSO induced cell cycle arrest and apoptosis in spheres,and diminished the expression of stemness genes.Moreover,treatment with either BSO or the glutathione recycling inhibitor 6-AN inhibited self-renewal and the expression of the CSC marker CD133.GSH content in spheres positively correlated with intrinsic resistance to gemcitabine treatment in different PDXs r=0.96,P=5.8×1011).Additionally,CD133+cells accumulated GSH in response to gemcitabine,which was abrogated by BSO treatment(P<0.05).Combined treatment with BSO and gemcitabine-induced apoptosis in CD133+cells to levels comparable to CD133-cells and significantly diminished self-renewal(P<0.05),suggesting that chemoresistance of CSCs is partially dependent on GSH metabolism.CONCLUSION Our data suggest that pancreatic CSCs depend on glutathione metabolism.Pharmacological targeting of this pathway showed that high GSH content is essential to maintain CSC functionality in terms of self-renewal and chemoresistance.展开更多
Breast cancer,like many other cancers,is believed to be driven by a population of cells that display stem cell properties.Recent studies suggest that cancer stem cells(CSCs)are essential for tumor progression,and tumo...Breast cancer,like many other cancers,is believed to be driven by a population of cells that display stem cell properties.Recent studies suggest that cancer stem cells(CSCs)are essential for tumor progression,and tumor relapse is thought to be caused by the presence of these cells.CSC-targeted therapies have also been proposed to overcome therapeutic resistance in breast cancer after the traditional therapies.Additionally,the metabolic properties of cancer cells differ markedly from those of normal cells.The efficacy of metabolic targeted therapy has been shown to enhance anti-cancer treatment or overcome therapeutic resistance of breast cancer cells.Metabolic targeting of breast CSCs(BCSCs)may be a very effective strategy for anti-cancer treatment of breast cancer cells.Thus,in this review,we focus on discussing the studies involving metabolism and targeted therapy in BCSCs.展开更多
The high mortality rate of breast cancer is mainly caused by the metastatic ability of cancer cells,resistance to chemotherapy and radiotherapy,and tumor regression capacity.In recent years,it has been shown that the ...The high mortality rate of breast cancer is mainly caused by the metastatic ability of cancer cells,resistance to chemotherapy and radiotherapy,and tumor regression capacity.In recent years,it has been shown that the presence of breast cancer stem cells is closely associated with the migration and metastatic ability of cancer cells,as well as with their resistance to chemotherapy and radiotherapy.The tumor microenvironment is one of the main molecular factors involved in cancer and metastatic processes development,in this sense it is interesting to study the role of platelets,one of the main communicator cells in the human body which are activated by the signals they receive from the microenvironment and can generate more than one response.Platelets can ingest and release RNA,proteins,cytokines and growth factors.After the platelets interact with the tumor microenvironment,they are called"tumor-educated platelets."Tumor-educated platelets transport material from the tumor microenvironment to sites adjacent to the tumor,thus helping to create microenvironments conducive for the development of primary and metastatic tumors.It has been observed that the clone capable of carrying out the metastatic process is a cancer cell with stem cell characteristics.Cancer stem cells go through a series of processes,including epithelial-mesenchymal transition,intravasation into blood vessels,movement through blood vessels,extravasation at the site of the establishment of a metastatic focus,and site colonization.Tumor-educated platelets support all these processes.展开更多
Gastric cancer(GC)is a primary cause of cancer-related mortality worldwide,and even after therapeutic gastrectomy,survival rates remain poor.The presence of gastric cancer stem cells(GCSCs)is thought to be the major r...Gastric cancer(GC)is a primary cause of cancer-related mortality worldwide,and even after therapeutic gastrectomy,survival rates remain poor.The presence of gastric cancer stem cells(GCSCs)is thought to be the major reason for resistance to anticancer treatment(chemotherapy or radiotherapy),and for the development of tumor recurrence,epithelial–mesenchymal transition,and metastases.Additionally,GCSCs have the capacity for self-renewal,differentiation,and tumor initiation.They also synthesize antiapoptotic factors,demonstrate higher performance of drug efflux pumps,and display cell plasticity abilities.Moreover,the tumor microenvironment(TME;tumor niche)that surrounds GCSCs contains secreted growth factors and supports angiogenesis and is thus responsible for the maintenance of the growing tumor.However,the genesis of GCSCs is unclear and exploration of the source of GCSCs is essential.In this review,we provide up-todate information about GCSC-surface/intracellular markers and GCSC-mediated pathways and their role in tumor development.This information will support improved diagnosis,novel therapeutic approaches,and better prognosis using GCSC-targeting agents as a potentially effective treatment choice following surgical resection or in combination with chemotherapy and radiotherapy.To date,most anti-GCSC blockers when used alone have been reported as unsatisfactory anticancer agents.However,when used in combination with adjuvant therapy,treatment can improve.By providing insights into the molecular mechanisms of GCSCs associated with tumors in GC,the aim is to optimize anti-GCSCs molecular approaches for GC therapy in combination with chemotherapy,radiotherapy,or other adjuvant treatment.展开更多
基金the National Natural Science Foundation of China,No.82074402the Science and Technology Innovation Project of China Academy of Chinese Medical Sciences,No.CI2021A01802.
文摘MicroRNAs(miRNAs)have received much attention in the past decade as potential key epigenomic regulators of tumors and cancer stem cells(CSCs).The abnormal expression of miRNAs is responsible for different phenotypes of gastric cancer stem cells(GCSCs).Some specific miRNAs could be used as promising biomarkers and therapeutic targets for the identification of GCSCs.This review summarizes the coding process and biological functions of miRNAs and demon-strates their role and efficacy in gastric cancer(GC)metastasis,drug resistance,and apoptosis,especially in the regulatory mechanism of GCSCs.It shows that the overexpression of onco-miRNAs and silencing of tumor-suppressor miRNAs can play a role in promoting or inhibiting tumor metastasis,apart from the initial formation of GC.It also discusses the epigenetic regulation and potential clinical applications of miRNAs as well as the role of CSCs in the pathogenesis of GC.We believe that this review may help in designing novel therapeutic approaches for GC.
基金Natural Science Foundation of Anhui Province(No.1908085MH258)Scientific Research and Innovation Project of Bengbu Medical College(No.Byycxz21004)。
文摘Objective:To explore the effect and mechanism of prostaglandins D2(PGD2)on the stemness of gastric cancer stem cells(GCSCs).Methods:7901-GCSCs were enriched by serum-free culture method;then the positivity rate of CD44,a stemness marker,was detected by flow cytometry in serum-free cultured 7901-GCSCs;the sphere-forming ability was detected by the sphere-forming assay after stimulation with different concentrations of PGD2(2.5,5,10)μg/mL,and the expression of stemness-related indicators(OCT4,CD44)and autophagyrelated proteins(LC3,Beclin-1)after PGD2 stimulation was detected by the western blot assay in different concentrations.The expression of stemness-related indexes(OCT4,CD44)and autophagy-related proteins(LC3,Beclin-1)were detected by Western blot assay after stimulation with different concentrations of PGD2.The expression of autophagy-related proteins after stimulation with different concentrations of CQ(2.5,5,10)μM was detected by Western blot experiment.The protein expression of autophagy-related proteins(LC3,Beclin-1)and stemness-related indexes(OCT4,CD44)was detected by Western blot experiment after PGD2 as well as PGD2+CQ treatment.Results:Flow cytometry results showed that the expression of CD44 positivity was increased in serum-free cultured 7901-GCSCs compared with gastric cancer cells SGC-7901(P<0.05),which fulfilled the needs of subsequent experiments.The results of stem cell spheroid formation assay showed that the spheroid formation ability of 7901-GCSCs in the PGD2 group was significantly weakened compared with that of the DMSO group(P<0.05).Western blot results showed that the protein expression of stemness-related indexes(OCT4,CD44)was down-regulated in the 7901-GCSCs in the PGD2 group compared with that of the DMSO group(P<0.05),and the expression of autophagy-related proteins(LC3,Beclin-1)expression increased(P<0.05).Compared with the DMSO group,the expression of autophagy-related proteins(LC3,Beclin-1)was decreased in the CQ group(P<0.05).Western blot results also showed that the expression of cellular autophagy-related proteins and stemness-related indexes in the PGD2+CQ group was not significantly changed compared with that of the DMSO group(ns:the difference was not significant),suggesting that the CQ could block the effect of PGD2 on the expression of stemness markers in 7901-GCSCs.7901-GCSCs stemness inhibition.Conclusion:PGD2 may affect the stemness of 7901-GCSCs by regulating autophagy.
基金supported by the Natural Science Foundation of Hubei Province(no.2021CFB372 to Hua Xiong).
文摘Lung cancer is the leading cause of cancer-related deaths globally.In recent years,with the widespread use of genetic testing,epidermal growth factor receptor–tyrosine kinase inhibitor(EGFR-TKI)–targeted drugs have been efficacious to patients with lung adenocarcinoma exhibiting EGFR mutations.However,resistance to treatment is inevitable and eventually leads to tumor progression,recurrence,and reduction in the overall treatment efficacy.Lung cancer stem cells play a crucial role in the development of resistance toward EGFR-TKI–targeted therapy for lung adenocarcinoma.Lung cancer stem cells possess self-renewal,multilineage differentiation,and unlimited proliferation capabilities,which efficiently contribute to tumor formation and ultimately lead to tumor recurrence andmetastasis.In this study,we evaluated the origin,markers,stemness index,relevant classic studies,resistance mechanisms,related signaling pathways,and strategies for reversing lung cancer stem cell resistance to EGFR-TKIs to provide new insights on delaying or reducing resistance and to improve the treatment efficacy of patients with EGFR-mutated lung adenocarcinoma in the future.
基金supported by the Department of Biotechnology(DBT),Govt of Indiasupported by the Council of Scientific and Industrial Research(CSIR),Govt.of India+1 种基金supported by the University Grants Commission(UGC),Govt.of Indiapartly supported by BT/INF/22/SP42155/2021 from the Department of Biotechnology,Ministry of Science and Technology,Govt.of India。
文摘Prostate cancer, one of the most frequently occurring cancers in men, is a heterogeneous disease involving multiple cell types within tumors. This tumor heterogeneity at least partly results from genomic instability leading to sub-clonal cellular differentiation. The differentiated cell populations originate from a small subset of cells with tumor-initiating and stem-like properties. These cells, termed prostate cancer stem cells(PCSCs), play crucial roles in disease progression, drug resistance, and relapse. This review discusses the origin, hierarchy, and plasticity of PCSCs;methods for isolation and enrichment of PCSCs;and various cellular and metabolic signaling pathways involved in PCSC induction and maintenance, as well as therapeutic targeting.
基金supported by the National Key Research and Development Program of China (Grant No.2023YFC3402100)the National Natural Science Foundation of China (Grant No.92259102)。
文摘Cancer stem cells(CSCs) are a small subset of cells in cancers that are thought to initiate tumorous transformation and promote metastasis, recurrence, and resistance to treatment. Growing evidence has revealed the existence of CSCs in various types of cancers and suggested that CSCs differentiate into diverse lineage cells that contribute to tumor progression. We may be able to overcome the limitations of cancer treatment with a comprehensive understanding of the biological features and mechanisms underlying therapeutic resistance in CSCs. This review provides an overview of the properties, biomarkers, and mechanisms of resistance shown by CSCs. Recent findings on metabolic features, especially fatty acid metabolism and ferroptosis in CSCs, are highlighted, along with promising targeting strategies. Targeting CSCs is a potential treatment plan to conquer cancer and prevent resistance and relapse in cancer treatment.
基金supported by grants from National Natural Science Foundation of China(Grant No.11832008)the Natural Scienceof Chongqing(Grant No.cstc2020jcyj-msxm X0545)the Japan Society for the Promotion of Science under grants-in-Aid for Scientific Research(S)(Grant No.17H06146)。
文摘Over the past 2 decades,cancer stem cells(CSCs)have been identified as the root cause of cancer occurrence,progression,chemoradioresistance,recurrence,and metastasis.Targeting CSCs is a novel therapeutic strategy for cancer management and treatment.Liver cancer(LC)is a malignant disease that can endanger human health.Studies are increasingly suggesting that changes in the liver mechanical microenvironment are a primary driver triggering the occurrence and development of liver cancer.In this review,we summarize current understanding of the roles of the liver mechano-microenvironment and liver cancer stem cells(LCSCs)in liver cancer progression.We also discuss the relationship between the mechanical heterogeneity of liver cancer tissues and LCSC recruitment and metastasis.Finally,we highlight potential mechanosensitive molecules in LCSCs and mechanotherapy in liver cancer.Understanding the roles and regulatory mechanisms of the mechano-microenvironment and LCSCs may provide fundamental insights into liver cancer progression and aid in further development of novel therapeutic strategies.
基金Natural Science Foundation of Nanjing University of Chinese Medicine China,No.XZR2020093.
文摘Cancer stem cells(CSCs)are a small proportion of the cells that exist in cancer tissues.They are considered to be the culprit of tumor genesis,development,drug resistance,metastasis and recurrence because of their self-renewal,proliferation,and differentiation potential.The elimination of CSCs is thus the key to cure cancer,and targeting CSCs provides a new method for tumor treatment.Due to the advantages of controlled sustained release,targeting and high biocompatibility,a variety of nanomaterials are used in the diagnosis and treatments targeting CSCs and promote the recognition and removal of tumor cells and CSCs.This article mainly reviews the research progress of nanotechnology in sorting CSCs and nanodrug delivery systems targeting CSCs.Furthermore,we identify the problems and future research directions of nanotechnology in CSC therapy.We hope that this review will provide guidance for the design of nanotechnology as a drug carrier so that it can be used in clinic for cancer therapy as soon as possible.
基金Supported by the Youth Medical Talent of Jiangsu Province,No.QNRC2016475.
文摘Cancer stem cells(CSCs)are the main cause of tumor growth,invasion,metastasis and recurrence.Recently,CSCs have been extensively studied to identify CSCspecific surface markers as well as signaling pathways that play key roles in CSCs self-renewal.The involvement of CSCs in the pathogenesis of gastrointestinal(GI)cancers also highlights these cells as a priority target for therapy.The diagnosis,prognosis and treatment of GI cancer have always been a focus of attention.Therefore,the potential application of CSCs in GI cancers is receiving increasing attention.This review summarizes the role of CSCs in GI cancers,focusing on esophageal cancer,gastric cancer,liver cancer,colorectal cancer,and pancreatic cancer.In addition,we propose CSCs as potential targets and therapeutic strategies for the effective treatment of GI cancers,which may provide better guidance for clinical treatment of GI cancers.
文摘Obesity,the global pandemic since industrialization,is the number one lifestylerelated risk factor for premature death,which increases the incidence and mortality of various diseases and conditions,including cancer.In recent years,the theory of cancer stem cells(CSCs),which have the capacity for self-renewal,metastasis and treatment resistance,has been bolstered by increasing evidence.However,research on how obesity affects CSCs to facilitate cancer initiation,progression and therapy resistance is still in its infancy,although evidence has already begun to accumulate.Regarding the ever-increasing burden of obesity and obesity-related cancer,it is pertinent to summarize evidence about the effects of obesity on CSCs,as elucidating these effects will contribute to the improvement in the management of obesity-related cancers.In this review,we discuss the association between obesity and CSCs,with a particular focus on how obesity promotes cancer initiation,progression and therapy resistance through CSCs and the mechanisms underlying these effects.In addition,the prospect of preventing cancer and targeting the mechanisms linking obesity and CSCs to reduce cancer risk or to improve the survival of patients with cancer is considered.
基金supported by ACTREC PhD fellowshipfunded by TMC-IRB (3542)ACTREC annual funds。
文摘Head and neck squamous cell carcinoma is the seventh most common cancer worldwide with high mortality rates.Amongst oral cavity cancers,tongue carcinoma is a very common and aggressive oral cavity carcinoma.Despite the implementation of a multimodality treatment regime including surgical intervention,chemo-radiation as well as targeted therapy,tongue carcinoma shows a poor overall 5-year survival pattern,which is attributed to therapy resistance and recurrence of the disease.The presence of a rare population,i.e.,cancer stem cells(CSCs)within the tumor,are involved in therapy resistance,recurrence,and distant metastasis that results in poor survival patterns.Therapeutic agents targeting CSCs have been in clinical trials,although they are unable to reach into therapy stage which is due to their failure in trials.A more detailed understanding of the CSCs is essential for identifying efficient targets.Molecular signaling pathways,which are differentially regulated in the CSCs,are one of the promising targets to manipulate the CSCs that would provide an improved outcome.In this review,we summarize the current understanding of molecular signaling associated with the maintenance and regulation of CSCs in tongue squamous cell carcinoma in order to emphasize the need of the hour to get a deeper understanding to unravel novel targets.
基金funded by Vietnam National Foundation for Science and Technology Development(NAFOSTED)under grant number 108.05-2017.331。
文摘Objective:To evaluate the effects of ethanol extract from Ardisia gigantifolia leaves on cell proliferation and cancer stem cell(CSC)number in gastric cancer.Methods:The inhibitory effect of Ardisia gigantifolia extract on the proliferation of MKN45 and MKN74 gastric cancer cells was assessed using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay.Non-adherent culture(3D)model was used to evaluate the effect of the extract on tumorsphere size and number.Moreover,the expression of CD44,ALDH,and p21 was determined by immunofluorescence analysis.Flow cytometric analysis was performed to evaluate cell cycle arrest and the expression of gastric CSC markers CD44 and ALDH.Real-time PCR analysis was also carried out to assess the effect of the extract on the expression of cell cycle-regulated genes.Results:Ardisia gigantifolia extract effectively inhibited cell proliferation with an IC_(50)of 55.7μg/m L in MKN45 cells and 123.6μg/m L in MKN74 cells.The extract also arrested cell cycle in the G_(0)/G_(1)phase as well as significantly reduced the size and number of tumorspheres.The markedly increased expression of p21 was observed at both m RNA and protein levels in the extract-treated adherent cells and tumorspheres.In addition,Ardisia gigantifolia extract significantly reduced the number of CD44-and/or ALDH-expressing gastric CSC.Conclusions:The development of gastric CSC can be inhibited by the ethanol extract of Ardisia gigantifolia.
基金Supported by UNAM-PAPIIT,No.IN219719 and No.IA205421CONACYT,No.A1-S-18285.
文摘Cancer stem cells(CSCs)are tumor cells that share functional characteristics with normal and embryonic stem cells.CSCs have increased tumor-initiating capacity and metastatic potential and lower sensitivity to chemo-and radiotherapy,with important roles in tumor progression and the response to therapy.Thus,a current goal of cancer research is to eliminate CSCs,necessitating an adequate phenotypic and functional characterization of CSCs.Strategies have been developed to identify,enrich,and track CSCs,many of which distinguish CSCs by evaluating the expression of surface markers,the initiation of specific signaling pathways,and the activation of master transcription factors that control stemness in normal cells.We review and discuss the use of reporter gene systems for identifying CSCs.Reporters that are under the control of aldehyde dehydrogenase 1A1,CD133,Notch,Nanog homeobox,Sex-determining region Y-box 2,and POU class 5 homeobox can be used to identify CSCs in many tumor types,track cells in real time,and screen for drugs.Thus,reporter gene systems,in combination with in vitro and in vivo functional assays,can assess changes in the CSCs pool.We present relevant examples of these systems in the evaluation of experimental CSCs-targeting therapeutics,demonstrating their value in CSCs research.
文摘The cancer stem cells(CSCs)from human osteosarcoma by serum-free three-dimensional culture combined with anticancer drugs were isolated and identified.The primary cells derived from human osteosarcoma were digested by trypsin to prepare a single-cell suspension,and mixed homogeneously into 1.2% alginate gel.Single-cell alginate gel was cultured with serum-free DMEM/F12 medium.Epirubicin(0.8μg/mL)was added to the medium to enrich CSCs.After cultured conventionally for 7 to 10 days,most of cells suspended in alginate gel were killed by epirubicin.But few cells survived and some single-cell cloning spheres formed.Immunofluorescent staining for Oct3/4 and Nanog was implemented to find cells with properties of self-renewal and multi-potential differentiation.Cells from cloning spheres were transplanted into BALB/c mice to detect the tumorigenicity in vivo.The results showed that some cells positive for Oct3/4(TRITC)and Nanog(TRITC)were found in single-cell cloning spheres,and most of positive cells were concentrated in the core of sphere.Cells from spheres could form osteosarcoma in the body of mice.It was concluded that cells from single-cell cloning spheres had the properties of the expression of parts of stem cell genes(Oct3/4 and Nanog),resisting anti-cancer drugs,and tumorigenicity in vivo.To sum up,it is believed that cells obtained from osteosarcoma by serum-free three-dimensional culture combined with anticancer drugs are cancer stem cells.
基金Supported by the National Natural Science Foundation of China,No.81272687the Natural Science Foundation of Zhejiang Province of China,No.LZ13H160004 and No.LY16H160056the 521 Talent Project of Zhejiang Sci-Tech University
文摘Gastrointestinal cancer has been one of the five most commonly diagnosed and leading causes of cancer mortality over the past few decades. Great progress in traditional therapies has been made, which prolonged survival in patients with early cancer, yet tumor relapse and drug resistance still occurred, which is explained by the cancer stem cell(CSC) theory. Oncolytic virotherapy has attracted increasing interest in cancer because of its ability to infect and lyse CSCs. This paper reviews the basic knowledge, CSC markers and therapeutics of gastrointestinal cancer(liver, gastric, colon and pancreatic cancer), as well as research advances and possible molecular mechanisms of various oncolytic viruses against gastrointestinal CSCs. This paper also summarizes the existing obstacles to oncolytic virotherapy and proposes several alternative suggestions to overcome the therapeutic limitations.
基金Supported by SERB:Department of Science and Technology,New Delhi,No. NPDF:SERB 2015/000322
文摘Epigenetic modifications have been observed as a decline in miRNA-21 expression and breast cancer stem cell(CSC)population after 3 cycles of standard chemotherapy.The epigenetic response(miRNAs expression)and CSCs are also correlated in patients with Breast Cancer.In patients who tolerated chemotherapy well,miRNA-21(non-coding RNA)expression decreased significantly after three cycles of chemotherapy.The miRNA-21 expression in breast cancer tissue was quantified by quantitative PCR(real-time PCR)using the standard protocol.In addition,breast CSCs(CD44+/CD24-)were also decreased in these patients.The miRNA-21 regulates cell division,proliferation,and autophagy of cancerous cells(as it targets phosphatase and tensin homolog/AKT/transcription factor EB/programmed cell death 4/autophagy-related protein 5 and chemotherapy also produces similar effects),thereby contributing to these benefits.Therefore,when all of the targets on genes have been explored by mimic miRNA,chemotherapy combined with anti-miRNA21 therapy may prove useful in the care of cancer patients.
文摘Autophagy is a highly regulated catabolic process in which superfluous,damaged organelles and other cytoplasmic constituents are delivered to the lysosome for clearance and the generation of macromolecule substrates during basal or stressed conditions.Autophagy is a bimodal process with a context dependent role in the initiation and the development of cancers.For instance,autophagy provides an adaptive response to cancer stem cells to survive metabolic stresses,by influencing disease propagation via modulation of essential signaling pathways or by promoting resistance to chemotherapeutics.Autophagy has been implicated in a cross talk with apoptosis.Understanding the complex interactions provides an opportunity to improve cancer therapy and the clinical outcome for the cancer patients.In this review,we provide a comprehensive view on the current knowledge on autophagy and its role in cancer cells with a particular focus on cancer stem cell homeostasis.
文摘BACKGROUND Cellular metabolism regulates stemness in health and disease.A reduced redox state is essential for self-renewal of normal and cancer stem cells(CSCs).However,while stem cells rely on glycolysis,different CSCs,including pancreatic CSCs,favor mitochondrial metabolism as their dominant energy-producing pathway.This suggests that powerful antioxidant networks must be in place to detoxify mitochondrial reactive oxygen species(ROS)and maintain stemness in oxidative CSCs.Since glutathione metabolism is critical for normal stem cell function and CSCs from breast,liver and gastric cancer show increased glutathione content,we hypothesized that pancreatic CSCs also rely on this pathway for ROS detoxification.AIM To investigate the role of glutathione metabolism in pancreatic CSCs.METHODS Primary pancreatic cancer cells of patient-derived xenografts(PDXs)were cultured in adherent or CSC-enriching sphere conditions to determine the role of glutathione metabolism in stemness.Real-time polymerase chain reaction(PCR)was used to validate RNAseq results involving glutathione metabolism genes in adherent vs spheres,as well as the expression of pluripotency-related genes following treatment.Public TCGA and GTEx RNAseq data from pancreatic cancer vs normal tissue samples were analyzed using the webserver GEPIA2.The glutathione-sensitive fluorescent probe monochlorobimane was used to determine glutathione content by fluorimetry or flow cytometry.Pharmacological inhibitors of glutathione synthesis and recycling[buthionine-sulfoximine(BSO)and 6-Aminonicotinamide(6-AN),respectively]were used to investigate the impact of glutathione depletion on CSC-enriched cultures.Staining with propidium iodide(cell cycle),Annexin-V(apoptosis)and CD133(CSC content)were determined by flow cytometry.Self-renewal was assessed by sphere formation assay and response to gemcitabine treatment was used as a readout for chemoresistance.RESULTS Analysis of our previously published RNAseq dataset E-MTAB-3808 revealed upregulation of genes involved in the KEGG(Kyoto Encyclopedia of Genes and Genomes)Pathway Glutathione Metabolism in CSC-enriched cultures compared to their differentiated counterparts.Consistently,in pancreatic cancer patient samples the expression of most of these up-regulated genes positively correlated with a stemness signature defined by NANOG,KLF4,SOX2 and OCT4 expression(P<10-5).Moreover,3 of the upregulated genes(MGST1,GPX8,GCCT)were associated with reduced disease-free survival in patients[Hazard ratio(HR)2.2-2.5;P=0.03-0.0054],suggesting a critical role for this pathway in pancreatic cancer progression.CSC-enriched sphere cultures also showed increased expression of different glutathione metabolism-related genes,as well as enhanced glutathione content in its reduced form(GSH).Glutathione depletion with BSO induced cell cycle arrest and apoptosis in spheres,and diminished the expression of stemness genes.Moreover,treatment with either BSO or the glutathione recycling inhibitor 6-AN inhibited self-renewal and the expression of the CSC marker CD133.GSH content in spheres positively correlated with intrinsic resistance to gemcitabine treatment in different PDXs r=0.96,P=5.8×1011).Additionally,CD133+cells accumulated GSH in response to gemcitabine,which was abrogated by BSO treatment(P<0.05).Combined treatment with BSO and gemcitabine-induced apoptosis in CD133+cells to levels comparable to CD133-cells and significantly diminished self-renewal(P<0.05),suggesting that chemoresistance of CSCs is partially dependent on GSH metabolism.CONCLUSION Our data suggest that pancreatic CSCs depend on glutathione metabolism.Pharmacological targeting of this pathway showed that high GSH content is essential to maintain CSC functionality in terms of self-renewal and chemoresistance.
文摘Breast cancer,like many other cancers,is believed to be driven by a population of cells that display stem cell properties.Recent studies suggest that cancer stem cells(CSCs)are essential for tumor progression,and tumor relapse is thought to be caused by the presence of these cells.CSC-targeted therapies have also been proposed to overcome therapeutic resistance in breast cancer after the traditional therapies.Additionally,the metabolic properties of cancer cells differ markedly from those of normal cells.The efficacy of metabolic targeted therapy has been shown to enhance anti-cancer treatment or overcome therapeutic resistance of breast cancer cells.Metabolic targeting of breast CSCs(BCSCs)may be a very effective strategy for anti-cancer treatment of breast cancer cells.Thus,in this review,we focus on discussing the studies involving metabolism and targeted therapy in BCSCs.
文摘The high mortality rate of breast cancer is mainly caused by the metastatic ability of cancer cells,resistance to chemotherapy and radiotherapy,and tumor regression capacity.In recent years,it has been shown that the presence of breast cancer stem cells is closely associated with the migration and metastatic ability of cancer cells,as well as with their resistance to chemotherapy and radiotherapy.The tumor microenvironment is one of the main molecular factors involved in cancer and metastatic processes development,in this sense it is interesting to study the role of platelets,one of the main communicator cells in the human body which are activated by the signals they receive from the microenvironment and can generate more than one response.Platelets can ingest and release RNA,proteins,cytokines and growth factors.After the platelets interact with the tumor microenvironment,they are called"tumor-educated platelets."Tumor-educated platelets transport material from the tumor microenvironment to sites adjacent to the tumor,thus helping to create microenvironments conducive for the development of primary and metastatic tumors.It has been observed that the clone capable of carrying out the metastatic process is a cancer cell with stem cell characteristics.Cancer stem cells go through a series of processes,including epithelial-mesenchymal transition,intravasation into blood vessels,movement through blood vessels,extravasation at the site of the establishment of a metastatic focus,and site colonization.Tumor-educated platelets support all these processes.
基金the Ministry of Science and Technology,Taiwan,No.MOST 108-2320-B-255-002-MY3Chang Gung Medical Research Foundation,Taoyuan,Taiwan No.CMRPF1I0031,No.CMRPF1I0041,No.CMRPF1I0041-2,and No.CMRPF1L0021and Chang Gung University of Science and Technology,Taoyuan,Taiwan,No.ZRRPF3J0081,No.ZRRPF3K0111,and No.ZRRPF3L0091.
文摘Gastric cancer(GC)is a primary cause of cancer-related mortality worldwide,and even after therapeutic gastrectomy,survival rates remain poor.The presence of gastric cancer stem cells(GCSCs)is thought to be the major reason for resistance to anticancer treatment(chemotherapy or radiotherapy),and for the development of tumor recurrence,epithelial–mesenchymal transition,and metastases.Additionally,GCSCs have the capacity for self-renewal,differentiation,and tumor initiation.They also synthesize antiapoptotic factors,demonstrate higher performance of drug efflux pumps,and display cell plasticity abilities.Moreover,the tumor microenvironment(TME;tumor niche)that surrounds GCSCs contains secreted growth factors and supports angiogenesis and is thus responsible for the maintenance of the growing tumor.However,the genesis of GCSCs is unclear and exploration of the source of GCSCs is essential.In this review,we provide up-todate information about GCSC-surface/intracellular markers and GCSC-mediated pathways and their role in tumor development.This information will support improved diagnosis,novel therapeutic approaches,and better prognosis using GCSC-targeting agents as a potentially effective treatment choice following surgical resection or in combination with chemotherapy and radiotherapy.To date,most anti-GCSC blockers when used alone have been reported as unsatisfactory anticancer agents.However,when used in combination with adjuvant therapy,treatment can improve.By providing insights into the molecular mechanisms of GCSCs associated with tumors in GC,the aim is to optimize anti-GCSCs molecular approaches for GC therapy in combination with chemotherapy,radiotherapy,or other adjuvant treatment.
