Proapoptotic Function of Integrin β3 in Human Hepatocellular Carcinoma Cells

Purpose: This study evaluates the proapoptotic function of integrin β 3 in human hepatocellular carcinoma (HCC). Experimental Design: The expression of integrin β 3 in 67 HCC specimens paired with corresponding neighboring nontumorous tissue was studied by quantitative real-time PCR and Western blot...

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Veröffentlicht in:Clinical cancer research 2009-01, Vol.15 (1), p.60-69
Hauptverfasser: Wu, Yanhua, Zuo, Jie, Ji, Guoqing, Saiyin, Hexige, Liu, Xing, Yin, Feiyu, Cao, Ning, Wen, Yunfei, Li, Jian Jian, Yu, Long
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container_end_page 69
container_issue 1
container_start_page 60
container_title Clinical cancer research
container_volume 15
creator Wu, Yanhua
Zuo, Jie
Ji, Guoqing
Saiyin, Hexige
Liu, Xing
Yin, Feiyu
Cao, Ning
Wen, Yunfei
Li, Jian Jian
Yu, Long
description Purpose: This study evaluates the proapoptotic function of integrin β 3 in human hepatocellular carcinoma (HCC). Experimental Design: The expression of integrin β 3 in 67 HCC specimens paired with corresponding neighboring nontumorous tissue was studied by quantitative real-time PCR and Western blot. The proapoptotic function of integrin β 3 in SMMC-7721 human hepatoma cells overexpressing ITGB3 (gene coding integrin β 3 ) was determined through colony formation, serum starvation, and anoikis assay. Results: Compared with neighboring pathologically normal liver tissue, ∼60% of the HCC specimens showed a significant down-regulated level of integrin β 3 expression. Transient expression of integrin β 3 in SMMC-7721 resulted in an enhanced level of apoptosis and suppression of colony formation. Cell growth inhibition on serum/ligand deprivation and incidences of anoikis were remarkably increased in SMMC-7721 with stable expression of integrin β 3 in comparison with vector control transfectants. In addition, expression of fibrinogen and vitronectin, two native ligands for integrin α v β 3 in liver, was inhibited, which was correlated with the decreased integrin β 3 expression. Replenishing these ligands to the starved SMMC-7721 stable transfectants effectively restored the proapoptotic function of integrin β 3 . Conclusions: Down-regulation of integrin β 3 and its ligands in liver is related to the aggressive growth of HCC. Thus, reconstitution of integrin β 3 in HCC may be a potential therapeutic approach to inhibit aggressive growth of liver cancer.
doi_str_mv 10.1158/1078-0432.CCR-08-1028
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Experimental Design: The expression of integrin β 3 in 67 HCC specimens paired with corresponding neighboring nontumorous tissue was studied by quantitative real-time PCR and Western blot. The proapoptotic function of integrin β 3 in SMMC-7721 human hepatoma cells overexpressing ITGB3 (gene coding integrin β 3 ) was determined through colony formation, serum starvation, and anoikis assay. Results: Compared with neighboring pathologically normal liver tissue, ∼60% of the HCC specimens showed a significant down-regulated level of integrin β 3 expression. Transient expression of integrin β 3 in SMMC-7721 resulted in an enhanced level of apoptosis and suppression of colony formation. Cell growth inhibition on serum/ligand deprivation and incidences of anoikis were remarkably increased in SMMC-7721 with stable expression of integrin β 3 in comparison with vector control transfectants. In addition, expression of fibrinogen and vitronectin, two native ligands for integrin α v β 3 in liver, was inhibited, which was correlated with the decreased integrin β 3 expression. Replenishing these ligands to the starved SMMC-7721 stable transfectants effectively restored the proapoptotic function of integrin β 3 . Conclusions: Down-regulation of integrin β 3 and its ligands in liver is related to the aggressive growth of HCC. Thus, reconstitution of integrin β 3 in HCC may be a potential therapeutic approach to inhibit aggressive growth of liver cancer.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-08-1028</identifier><identifier>PMID: 19118033</identifier><language>eng</language><publisher>American Association for Cancer Research</publisher><subject>anoikis ; extracellular matrix ; hepatocellular carcinoma ; integrin ; tumorigenesis</subject><ispartof>Clinical cancer research, 2009-01, Vol.15 (1), p.60-69</ispartof><rights>2009 American Association for Cancer Research 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c382t-129f3748d5f7bfe31dd563cd17f65d4efa8a381d51f67877e904a756cec78f303</citedby><cites>FETCH-LOGICAL-c382t-129f3748d5f7bfe31dd563cd17f65d4efa8a381d51f67877e904a756cec78f303</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,3343,27901,27902</link.rule.ids></links><search><creatorcontrib>Wu, Yanhua</creatorcontrib><creatorcontrib>Zuo, Jie</creatorcontrib><creatorcontrib>Ji, Guoqing</creatorcontrib><creatorcontrib>Saiyin, Hexige</creatorcontrib><creatorcontrib>Liu, Xing</creatorcontrib><creatorcontrib>Yin, Feiyu</creatorcontrib><creatorcontrib>Cao, Ning</creatorcontrib><creatorcontrib>Wen, Yunfei</creatorcontrib><creatorcontrib>Li, Jian Jian</creatorcontrib><creatorcontrib>Yu, Long</creatorcontrib><title>Proapoptotic Function of Integrin β3 in Human Hepatocellular Carcinoma Cells</title><title>Clinical cancer research</title><description>Purpose: This study evaluates the proapoptotic function of integrin β 3 in human hepatocellular carcinoma (HCC). Experimental Design: The expression of integrin β 3 in 67 HCC specimens paired with corresponding neighboring nontumorous tissue was studied by quantitative real-time PCR and Western blot. The proapoptotic function of integrin β 3 in SMMC-7721 human hepatoma cells overexpressing ITGB3 (gene coding integrin β 3 ) was determined through colony formation, serum starvation, and anoikis assay. Results: Compared with neighboring pathologically normal liver tissue, ∼60% of the HCC specimens showed a significant down-regulated level of integrin β 3 expression. Transient expression of integrin β 3 in SMMC-7721 resulted in an enhanced level of apoptosis and suppression of colony formation. Cell growth inhibition on serum/ligand deprivation and incidences of anoikis were remarkably increased in SMMC-7721 with stable expression of integrin β 3 in comparison with vector control transfectants. In addition, expression of fibrinogen and vitronectin, two native ligands for integrin α v β 3 in liver, was inhibited, which was correlated with the decreased integrin β 3 expression. Replenishing these ligands to the starved SMMC-7721 stable transfectants effectively restored the proapoptotic function of integrin β 3 . Conclusions: Down-regulation of integrin β 3 and its ligands in liver is related to the aggressive growth of HCC. Thus, reconstitution of integrin β 3 in HCC may be a potential therapeutic approach to inhibit aggressive growth of liver cancer.</description><subject>anoikis</subject><subject>extracellular matrix</subject><subject>hepatocellular carcinoma</subject><subject>integrin</subject><subject>tumorigenesis</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><recordid>eNpVkM1KxDAUhYMozjj6CEJX7jrmNs3PbAQpjjOgKKLrkEmTaaRNStpRfC0fxGeyZVRwc8_l3HvO4kPoHPAcgIpLwFykOCfZvCieUixSwJk4QFOglKckY_Rw2H9_Juik614xhhxwfowmsAAQmJApun-MQbWh7UPvdLLced274JNgk7XvzTY6n3x9kmSQ1a5RwzSt6oM2db2rVUwKFbXzoVFJMVjdKTqyqu7M2Y_O0Mvy5rlYpXcPt-vi-i7VRGR9CtnCEp6Lklq-sYZAWVJGdAncMlrmxiqhiICSgmVccG4WOFecMm00F5ZgMkNX-952t2lMqY3vo6plG12j4ocMysn_F-8quQ1vkjAqGLChgO4LdAxdF439ywKWI185spMjOznwlXg0MjHkLva5ym2rdxeN1MprE6PpzICikkAlSIbJNy9wfJE</recordid><startdate>20090101</startdate><enddate>20090101</enddate><creator>Wu, Yanhua</creator><creator>Zuo, Jie</creator><creator>Ji, Guoqing</creator><creator>Saiyin, Hexige</creator><creator>Liu, Xing</creator><creator>Yin, Feiyu</creator><creator>Cao, Ning</creator><creator>Wen, Yunfei</creator><creator>Li, Jian Jian</creator><creator>Yu, Long</creator><general>American Association for Cancer Research</general><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20090101</creationdate><title>Proapoptotic Function of Integrin β3 in Human Hepatocellular Carcinoma Cells</title><author>Wu, Yanhua ; Zuo, Jie ; Ji, Guoqing ; Saiyin, Hexige ; Liu, Xing ; Yin, Feiyu ; Cao, Ning ; Wen, Yunfei ; Li, Jian Jian ; Yu, Long</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c382t-129f3748d5f7bfe31dd563cd17f65d4efa8a381d51f67877e904a756cec78f303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>anoikis</topic><topic>extracellular matrix</topic><topic>hepatocellular carcinoma</topic><topic>integrin</topic><topic>tumorigenesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Yanhua</creatorcontrib><creatorcontrib>Zuo, Jie</creatorcontrib><creatorcontrib>Ji, Guoqing</creatorcontrib><creatorcontrib>Saiyin, Hexige</creatorcontrib><creatorcontrib>Liu, Xing</creatorcontrib><creatorcontrib>Yin, Feiyu</creatorcontrib><creatorcontrib>Cao, Ning</creatorcontrib><creatorcontrib>Wen, Yunfei</creatorcontrib><creatorcontrib>Li, Jian Jian</creatorcontrib><creatorcontrib>Yu, Long</creatorcontrib><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Yanhua</au><au>Zuo, Jie</au><au>Ji, Guoqing</au><au>Saiyin, Hexige</au><au>Liu, Xing</au><au>Yin, Feiyu</au><au>Cao, Ning</au><au>Wen, Yunfei</au><au>Li, Jian Jian</au><au>Yu, Long</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Proapoptotic Function of Integrin β3 in Human Hepatocellular Carcinoma Cells</atitle><jtitle>Clinical cancer research</jtitle><date>2009-01-01</date><risdate>2009</risdate><volume>15</volume><issue>1</issue><spage>60</spage><epage>69</epage><pages>60-69</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: This study evaluates the proapoptotic function of integrin β 3 in human hepatocellular carcinoma (HCC). 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source American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
subjects anoikis
extracellular matrix
hepatocellular carcinoma
integrin
tumorigenesis
title Proapoptotic Function of Integrin β3 in Human Hepatocellular Carcinoma Cells
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