The blood-brain barrier is a unique property of central nervous system blood vessels that protects sensitive central nervous system cells from potentially harmful blood components.The mechanistic basis of this barrier...The blood-brain barrier is a unique property of central nervous system blood vessels that protects sensitive central nervous system cells from potentially harmful blood components.The mechanistic basis of this barrier is found at multiple levels,including the adherens and tight junction proteins that tightly bind adjacent endothelial cells and the influence of neighboring pericytes,microglia,and astrocyte endfeet.In addition,extracellular matrix components of the vascular basement membrane play a critical role in establishing and maintaining blood-brain barrier integrity,not only by providing an adhesive substrate for blood-brain barrier cells to adhere to,but also by providing guidance cues that strongly influence vascular cell behavior.The extracellular matrix protein laminin is one of the most abundant components of the basement membrane,and several lines of evidence suggest that it plays a key role in directing blood-brain barrier behavior.In this review,we describe the basic structure of laminin and its receptors,the expression patterns of these molecules in central nervous system blood vessels and how they are altered in disease states,and most importantly,how genetic deletion of different laminin isoforms or their receptors reveals the contribution of these molecules to blood-brain barrier function and integrity.Finally,we discuss some of the important unanswered questions in the field and provide a“to-do”list of some of the critical outstanding experiments.展开更多
AIM： To clarify the clinicopathological significance of laminin-5 y2 （LNγ2） and 133 （LNI33） chains and MMP7 expression in biliary tract cancer. METHODS： We analyzed the association between immunohistochemically...AIM： To clarify the clinicopathological significance of laminin-5 y2 （LNγ2） and 133 （LNI33） chains and MMP7 expression in biliary tract cancer. METHODS： We analyzed the association between immunohistochemically detected LNγ2, LNβ3, and MMP7 expression in biliary tract cancer and clinicopathological characteristics. Activity of MMP7 was analyzed by casein zymography. An in vitro invasion assay after treatment with MMP7-specific siRNA was performed. RESULTS： LNγ2 expression was predominantly observed in carcinoma cells at the invasive front. LNγ2 expression was seen in 57% of patients with biliary tract cancer, and was associated with depth of invasion, histologic type, and advanced stage. The expression pattern of LNβ3 was classified Into two types： invasive front dominant type （38%） and diffuse type （28%）.The invasive front dominant type was associated with histologic type and advanced stage. MMP7 positivity was correlated with LNγ2 or LNβ3 expression but not with clinicopathological characteristics. Active MMP7 detected by casein zymography was correlated with depth of invasion and advanced stage. Downregulation of MMP7 expression by siRNA resulted in a significant decrease in biliary tract cancer cell invasion in vitro.CONCLUSION： Our results suggest that LNγ2 and LNβ3, in conjunction with MMP7, play a key role in the progression of biliary tract cancer.展开更多
目的:研究lam in in和survivin蛋白在原发性胆囊癌组织中的表达情况,及其与癌组织类型、病理分级和转移状况的关系。方法:应用免疫组织化学方法检测49例原发性胆囊癌、21例胆囊腺瘤和13例慢性胆囊炎组织中lam in in和survivin蛋白的表...目的:研究lam in in和survivin蛋白在原发性胆囊癌组织中的表达情况,及其与癌组织类型、病理分级和转移状况的关系。方法:应用免疫组织化学方法检测49例原发性胆囊癌、21例胆囊腺瘤和13例慢性胆囊炎组织中lam in in和survivin蛋白的表达。结果:胆囊黏膜内癌或原位癌细胞基底膜lam in in线性染色完整;NevinⅡ期胆囊癌组织表现为基底膜不完整,变薄,断裂,或缺损;临床NevinⅢ、Ⅳ、Ⅴ期胆囊癌,则无基底膜形成,在肿瘤组织周围,lam in in表达类型呈碎片状或断线状和连续线状,部分癌组织内lam in in染色消失和癌细胞浆内有lam in in弱染色。胆囊癌组织中survivin阳性表达率明显高于胆囊腺瘤和慢性胆囊炎组织,但survivin的阳性表达与胆囊癌细胞分化程度、病理分级和转移无关(P>0.05)。且胆囊癌组织中lam in in的连续线断裂或缺失,与胆囊癌组织中survivin的表达情况无相关性。结论:胆囊癌基质中lam in in的表达类型与胆囊癌的侵袭和转移有关,而survivin在胆囊癌中表达增加,但两者之间似乎无关联。展开更多
Our previous reports have shown that lamininglycopeptides (LN-GPs), the total glycopeptides prepared from laminin (LN), can prevent the experimental lung metastasis and liver metastasis of mouse cancer cells. In order...Our previous reports have shown that lamininglycopeptides (LN-GPs), the total glycopeptides prepared from laminin (LN), can prevent the experimental lung metastasis and liver metastasis of mouse cancer cells. In order to explore the anti-metastatic mechanism of LNGPs, we studied the effects of LN-GPs on metastasisrelated behaviors of cancer cells in vitro. LN-GPs did not affect cell survival. However, LN-GPs inhibited cell attachment and spreading Of 5180 cells on LN- and Matrigelsubstrate in dose-dependent and time-dependent manners. Moreover, inhibition of cen attachment and spreading on Matrigel substrates were much greater on Matrigel substrate than on LN substrate. In the presence of LN-GPs, 5180 cells on LN substrate changed from a flattened polygonal shape to a round one, the migration of 5180 cells on LN substrate decreased, and the number of a highly invasive human pulmonary giant caxcinoma PG cells invading Matrigel filter in a Boyden chamber was reduced. LN-GPs thus have multiple inhibitory effects on cancer motastasisrelated behaviors.展开更多
Laminin receptor(LN-R, Mr=70,000) isolated from murine Lewis lung carcinoma was shown to be a single band on SDS-PAGE (Sodium Dodecyl Sulfate-Polyacrylamide gel electrophoresis) after reduction. The present study Indi...Laminin receptor(LN-R, Mr=70,000) isolated from murine Lewis lung carcinoma was shown to be a single band on SDS-PAGE (Sodium Dodecyl Sulfate-Polyacrylamide gel electrophoresis) after reduction. The present study Indicates that LN-R was a kind of glycoproteins by periodic add Schiff staining. It's pI was 4. 93. LN-R preperation was associated with phospholipid and neutral glycolipid by TLC (thin layer chromatography) or HPTLC (high performance thin layer chromtography) of chloroform-methanol extracts of LN-R, respectively, but without acidic glycolipid. Binding of LN-R with its ligand, Lamlnin, depended on the presence of Ca+ + , Mg++. LN-R may bind to actin.展开更多
文摘The blood-brain barrier is a unique property of central nervous system blood vessels that protects sensitive central nervous system cells from potentially harmful blood components.The mechanistic basis of this barrier is found at multiple levels,including the adherens and tight junction proteins that tightly bind adjacent endothelial cells and the influence of neighboring pericytes,microglia,and astrocyte endfeet.In addition,extracellular matrix components of the vascular basement membrane play a critical role in establishing and maintaining blood-brain barrier integrity,not only by providing an adhesive substrate for blood-brain barrier cells to adhere to,but also by providing guidance cues that strongly influence vascular cell behavior.The extracellular matrix protein laminin is one of the most abundant components of the basement membrane,and several lines of evidence suggest that it plays a key role in directing blood-brain barrier behavior.In this review,we describe the basic structure of laminin and its receptors,the expression patterns of these molecules in central nervous system blood vessels and how they are altered in disease states,and most importantly,how genetic deletion of different laminin isoforms or their receptors reveals the contribution of these molecules to blood-brain barrier function and integrity.Finally,we discuss some of the important unanswered questions in the field and provide a“to-do”list of some of the critical outstanding experiments.
基金Supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture,Sports,Science and Technology of Japan (H.Y. and K.I.)Grants-in-Aid for Cancer Research and for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health,Labor and Welfare of Japan (H.Y. and K.I.)
文摘AIM： To clarify the clinicopathological significance of laminin-5 y2 （LNγ2） and 133 （LNI33） chains and MMP7 expression in biliary tract cancer. METHODS： We analyzed the association between immunohistochemically detected LNγ2, LNβ3, and MMP7 expression in biliary tract cancer and clinicopathological characteristics. Activity of MMP7 was analyzed by casein zymography. An in vitro invasion assay after treatment with MMP7-specific siRNA was performed. RESULTS： LNγ2 expression was predominantly observed in carcinoma cells at the invasive front. LNγ2 expression was seen in 57% of patients with biliary tract cancer, and was associated with depth of invasion, histologic type, and advanced stage. The expression pattern of LNβ3 was classified Into two types： invasive front dominant type （38%） and diffuse type （28%）.The invasive front dominant type was associated with histologic type and advanced stage. MMP7 positivity was correlated with LNγ2 or LNβ3 expression but not with clinicopathological characteristics. Active MMP7 detected by casein zymography was correlated with depth of invasion and advanced stage. Downregulation of MMP7 expression by siRNA resulted in a significant decrease in biliary tract cancer cell invasion in vitro.CONCLUSION： Our results suggest that LNγ2 and LNβ3, in conjunction with MMP7, play a key role in the progression of biliary tract cancer.
文摘目的:研究lam in in和survivin蛋白在原发性胆囊癌组织中的表达情况,及其与癌组织类型、病理分级和转移状况的关系。方法:应用免疫组织化学方法检测49例原发性胆囊癌、21例胆囊腺瘤和13例慢性胆囊炎组织中lam in in和survivin蛋白的表达。结果:胆囊黏膜内癌或原位癌细胞基底膜lam in in线性染色完整;NevinⅡ期胆囊癌组织表现为基底膜不完整,变薄,断裂,或缺损;临床NevinⅢ、Ⅳ、Ⅴ期胆囊癌,则无基底膜形成,在肿瘤组织周围,lam in in表达类型呈碎片状或断线状和连续线状,部分癌组织内lam in in染色消失和癌细胞浆内有lam in in弱染色。胆囊癌组织中survivin阳性表达率明显高于胆囊腺瘤和慢性胆囊炎组织,但survivin的阳性表达与胆囊癌细胞分化程度、病理分级和转移无关(P>0.05)。且胆囊癌组织中lam in in的连续线断裂或缺失,与胆囊癌组织中survivin的表达情况无相关性。结论:胆囊癌基质中lam in in的表达类型与胆囊癌的侵袭和转移有关,而survivin在胆囊癌中表达增加,但两者之间似乎无关联。
文摘Our previous reports have shown that lamininglycopeptides (LN-GPs), the total glycopeptides prepared from laminin (LN), can prevent the experimental lung metastasis and liver metastasis of mouse cancer cells. In order to explore the anti-metastatic mechanism of LNGPs, we studied the effects of LN-GPs on metastasisrelated behaviors of cancer cells in vitro. LN-GPs did not affect cell survival. However, LN-GPs inhibited cell attachment and spreading Of 5180 cells on LN- and Matrigelsubstrate in dose-dependent and time-dependent manners. Moreover, inhibition of cen attachment and spreading on Matrigel substrates were much greater on Matrigel substrate than on LN substrate. In the presence of LN-GPs, 5180 cells on LN substrate changed from a flattened polygonal shape to a round one, the migration of 5180 cells on LN substrate decreased, and the number of a highly invasive human pulmonary giant caxcinoma PG cells invading Matrigel filter in a Boyden chamber was reduced. LN-GPs thus have multiple inhibitory effects on cancer motastasisrelated behaviors.
文摘Laminin receptor(LN-R, Mr=70,000) isolated from murine Lewis lung carcinoma was shown to be a single band on SDS-PAGE (Sodium Dodecyl Sulfate-Polyacrylamide gel electrophoresis) after reduction. The present study Indicates that LN-R was a kind of glycoproteins by periodic add Schiff staining. It's pI was 4. 93. LN-R preperation was associated with phospholipid and neutral glycolipid by TLC (thin layer chromatography) or HPTLC (high performance thin layer chromtography) of chloroform-methanol extracts of LN-R, respectively, but without acidic glycolipid. Binding of LN-R with its ligand, Lamlnin, depended on the presence of Ca+ + , Mg++. LN-R may bind to actin.
