Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain,such as a heparan,dermatan,chondroitin,or keratan sulfate,covalently attached to the protein core.These molecules arecategorized...Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain,such as a heparan,dermatan,chondroitin,or keratan sulfate,covalently attached to the protein core.These molecules arecategorized based on their structure,localization,and function,and can be found in the extracellular matrix,on the cell surface,and in the cytoplasm.Cell-surface heparan sulfate proteoglycans,such as syndecans,are the primary type present in healthy liver tissue.However,deterioration of the liver results in overproduction of other proteoglycan types.The purpose of this article is to provide a current summary of the most relevant data implicating proteoglycans in the development and progression of human and experimental liver cancer.A review of our work and other studies in the literature indicate that deterioration of liver function is accompanied by an increase in the amount of chondroitin sulfate proteoglycans.The alteration of proteoglycan composition interferes with the physiologic function of the liver on several levels.This article details and discusses the roles of syndecan-1,glypicans,agrin,perlecan,collagen XVIII/endostatin,endocan,serglycin,decorin,biglycan,asporin,fibromodulin,lumican,and versican in liver function.Specifically,glypicans,agrin,and versican play significant roles in the development of liver cancer.Conversely,the presence of decorin could potentially provide protective effects.展开更多
Background:It remains unclear if the vascular and connective tissue structures of primary and metastatic tumors are intrinsically determined or whether these characteristics are defined by the host tissue.Therefore we...Background:It remains unclear if the vascular and connective tissue structures of primary and metastatic tumors are intrinsically determined or whether these characteristics are defined by the host tissue.Therefore we examined the microanatomical steps of vasculature and connective tissue development of C38 colon carcinoma in different tissues.Methods:Tumors produced in mice at five different locations(the cecal wall,skin,liver,lung,and brain)were ana-lyzed using fluorescent immunohistochemistry,electron microscopy and quantitative real-time polymerase chain reaction.Results:We found that in the cecal wall,skin,liver,and lung,resident fibroblasts differentiate into collagenous matrix-producing myofibroblasts at the tumor periphery.These activated fibroblasts together with the produced matrix were incorporated by the tumor.The connective tissue development culminated in the appearance of intratumoral tissue columns(centrally located single microvessels embedded in connective tissue and smooth muscle actin-expressing myofibroblasts surrounded by basement membrane).Conversely,in the brain(which lacks fibroblasts),C38 metasta-ses only induced the development of vascularized desmoplastic tissue columns when the growing tumor reached the fibroblast-containing meninges.Conclusions:Our data suggest that the desmoplastic host tissue response is induced by tumor-derived fibrogenic molecules acting on host tissue fibroblasts.We concluded that not only the host tissue characteristics but also the tumor-derived fibrogenic signals determine the vascular and connective tissue structure of tumors.展开更多
基金Supported by Hungarian Research Fund(OTKA)(No.100904 to Kovalszky Iand No.105763 to Baghy K)
文摘Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain,such as a heparan,dermatan,chondroitin,or keratan sulfate,covalently attached to the protein core.These molecules arecategorized based on their structure,localization,and function,and can be found in the extracellular matrix,on the cell surface,and in the cytoplasm.Cell-surface heparan sulfate proteoglycans,such as syndecans,are the primary type present in healthy liver tissue.However,deterioration of the liver results in overproduction of other proteoglycan types.The purpose of this article is to provide a current summary of the most relevant data implicating proteoglycans in the development and progression of human and experimental liver cancer.A review of our work and other studies in the literature indicate that deterioration of liver function is accompanied by an increase in the amount of chondroitin sulfate proteoglycans.The alteration of proteoglycan composition interferes with the physiologic function of the liver on several levels.This article details and discusses the roles of syndecan-1,glypicans,agrin,perlecan,collagen XVIII/endostatin,endocan,serglycin,decorin,biglycan,asporin,fibromodulin,lumican,and versican in liver function.Specifically,glypicans,agrin,and versican play significant roles in the development of liver cancer.Conversely,the presence of decorin could potentially provide protective effects.
基金KD is the recipient of the Bolyai fellowship of the Hungarian Academy of Sciences and received support from the National Excellence Program(TÁMOP 4.2.4.A/1-11-1-2012-0001)BD acknowledges support from the Hungarian NRDI Office(K109626,K108465,KNN121510 and SNN114490)+2 种基金SP and VL acknowledge support from the Hungarian NRDI Office(ANN125583)JT acknowledges support from the National Research,Development and Innovation Office(NKFIH116295)EB is the recipient of postdoctoral fellowship from the Hungarian Academy of Sciences.
文摘Background:It remains unclear if the vascular and connective tissue structures of primary and metastatic tumors are intrinsically determined or whether these characteristics are defined by the host tissue.Therefore we examined the microanatomical steps of vasculature and connective tissue development of C38 colon carcinoma in different tissues.Methods:Tumors produced in mice at five different locations(the cecal wall,skin,liver,lung,and brain)were ana-lyzed using fluorescent immunohistochemistry,electron microscopy and quantitative real-time polymerase chain reaction.Results:We found that in the cecal wall,skin,liver,and lung,resident fibroblasts differentiate into collagenous matrix-producing myofibroblasts at the tumor periphery.These activated fibroblasts together with the produced matrix were incorporated by the tumor.The connective tissue development culminated in the appearance of intratumoral tissue columns(centrally located single microvessels embedded in connective tissue and smooth muscle actin-expressing myofibroblasts surrounded by basement membrane).Conversely,in the brain(which lacks fibroblasts),C38 metasta-ses only induced the development of vascularized desmoplastic tissue columns when the growing tumor reached the fibroblast-containing meninges.Conclusions:Our data suggest that the desmoplastic host tissue response is induced by tumor-derived fibrogenic molecules acting on host tissue fibroblasts.We concluded that not only the host tissue characteristics but also the tumor-derived fibrogenic signals determine the vascular and connective tissue structure of tumors.
