Caveolin-1 Regulating the Invasion and Expression of Matrix Metalloproteinase (MMPs) in Pancreatic Carcinoma Cells

The gelatinases B (MMP9) and A (MMP2) are two members of the matrix metalloproteinase (MMPs) family that are expressed in human cancer, and play a critical role in tumor cell invasion and metastasis. Caveolin-1 (Cav1) has recently been identified as a tumor metastasis modifier gene. However, the eff...

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Veröffentlicht in:The Journal of surgical research 2010-03, Vol.159 (1), p.443-450
Hauptverfasser: Han, Fei, Ph.D, Zhu, Hong-Guang, Ph.D., M.D
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Zhu, Hong-Guang, Ph.D., M.D
description The gelatinases B (MMP9) and A (MMP2) are two members of the matrix metalloproteinase (MMPs) family that are expressed in human cancer, and play a critical role in tumor cell invasion and metastasis. Caveolin-1 (Cav1) has recently been identified as a tumor metastasis modifier gene. However, the effect and mechanism of Cav1 in pancreatic carcinoma cell invasion remain unknown. In this study, we investigated the expression of Cav1, MMP2, and MMP9 in several different pancreatic carcinoma cell lines. We transfected pcDNA3.0-Cav1 plasmid and Cav1 siRNA into SW1990 and Bxpc3 cells, respectively. Using cell invasion assay, we found that overexpression of Cav1 inhibited cell invasion, whereas the knockdown of Cav1 in Bxpc3 cells promoted cell invasion. Moreover, to explore the mechanisms underlying these observations, we further investigated the expression of MMP2, MMP9, phospho-Akt, and phospho-Erk by Western blot, and the activities of MMP2 and MMP9 by gelatin zymography. The results indicated that Cav1 gene could inhibit pancreatic carcinoma cell invasion, at least in part, probably through Erk-MMP signal pathway, suggesting that the endogenous expression or re-expression of Cav1 might help therapeutically reduce their invasive potential in pancreatic carcinoma cells.
doi_str_mv 10.1016/j.jss.2009.03.079
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Caveolin-1 (Cav1) has recently been identified as a tumor metastasis modifier gene. However, the effect and mechanism of Cav1 in pancreatic carcinoma cell invasion remain unknown. In this study, we investigated the expression of Cav1, MMP2, and MMP9 in several different pancreatic carcinoma cell lines. We transfected pcDNA3.0-Cav1 plasmid and Cav1 siRNA into SW1990 and Bxpc3 cells, respectively. Using cell invasion assay, we found that overexpression of Cav1 inhibited cell invasion, whereas the knockdown of Cav1 in Bxpc3 cells promoted cell invasion. Moreover, to explore the mechanisms underlying these observations, we further investigated the expression of MMP2, MMP9, phospho-Akt, and phospho-Erk by Western blot, and the activities of MMP2 and MMP9 by gelatin zymography. The results indicated that Cav1 gene could inhibit pancreatic carcinoma cell invasion, at least in part, probably through Erk-MMP signal pathway, suggesting that the endogenous expression or re-expression of Cav1 might help therapeutically reduce their invasive potential in pancreatic carcinoma cells.</description><identifier>ISSN: 0022-4804</identifier><identifier>EISSN: 1095-8673</identifier><identifier>DOI: 10.1016/j.jss.2009.03.079</identifier><identifier>PMID: 20031158</identifier><identifier>CODEN: JSGRA2</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Biological and medical sciences ; Carcinoma - enzymology ; Caveolin 1 - genetics ; Caveolin 1 - metabolism ; caveolin-1 ; Cell Line, Tumor ; Chromones ; Epithelial Cells - enzymology ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Flavonoids ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene Knockdown Techniques ; General aspects ; Humans ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; MAP Kinase Signaling System ; matrix metalloproteinase ; Matrix Metalloproteinase 2 - metabolism ; Matrix Metalloproteinase 2 - secretion ; Matrix Metalloproteinase 9 - metabolism ; Matrix Metalloproteinase 9 - secretion ; Medical sciences ; Mitogen-Activated Protein Kinase Kinases - antagonists &amp; inhibitors ; Morpholines ; Neoplasm Invasiveness ; pancreatic carcinoma ; Pancreatic Ducts - enzymology ; Pancreatic Neoplasms - enzymology ; Phosphatidylinositol 3-Kinases - antagonists &amp; inhibitors ; Proto-Oncogene Proteins c-akt - metabolism ; RNA Interference ; RNA, Messenger - metabolism ; RNA, Small Interfering - metabolism ; Surgery ; Tumors</subject><ispartof>The Journal of surgical research, 2010-03, Vol.159 (1), p.443-450</ispartof><rights>2010</rights><rights>2015 INIST-CNRS</rights><rights>Copyright (c) 2010. Published by Elsevier Inc. 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Caveolin-1 (Cav1) has recently been identified as a tumor metastasis modifier gene. However, the effect and mechanism of Cav1 in pancreatic carcinoma cell invasion remain unknown. In this study, we investigated the expression of Cav1, MMP2, and MMP9 in several different pancreatic carcinoma cell lines. We transfected pcDNA3.0-Cav1 plasmid and Cav1 siRNA into SW1990 and Bxpc3 cells, respectively. Using cell invasion assay, we found that overexpression of Cav1 inhibited cell invasion, whereas the knockdown of Cav1 in Bxpc3 cells promoted cell invasion. Moreover, to explore the mechanisms underlying these observations, we further investigated the expression of MMP2, MMP9, phospho-Akt, and phospho-Erk by Western blot, and the activities of MMP2 and MMP9 by gelatin zymography. The results indicated that Cav1 gene could inhibit pancreatic carcinoma cell invasion, at least in part, probably through Erk-MMP signal pathway, suggesting that the endogenous expression or re-expression of Cav1 might help therapeutically reduce their invasive potential in pancreatic carcinoma cells.</description><subject>Biological and medical sciences</subject><subject>Carcinoma - enzymology</subject><subject>Caveolin 1 - genetics</subject><subject>Caveolin 1 - metabolism</subject><subject>caveolin-1</subject><subject>Cell Line, Tumor</subject><subject>Chromones</subject><subject>Epithelial Cells - enzymology</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Flavonoids</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene Knockdown Techniques</subject><subject>General aspects</subject><subject>Humans</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>MAP Kinase Signaling System</subject><subject>matrix metalloproteinase</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Matrix Metalloproteinase 2 - secretion</subject><subject>Matrix Metalloproteinase 9 - metabolism</subject><subject>Matrix Metalloproteinase 9 - secretion</subject><subject>Medical sciences</subject><subject>Mitogen-Activated Protein Kinase Kinases - antagonists &amp; inhibitors</subject><subject>Morpholines</subject><subject>Neoplasm Invasiveness</subject><subject>pancreatic carcinoma</subject><subject>Pancreatic Ducts - enzymology</subject><subject>Pancreatic Neoplasms - enzymology</subject><subject>Phosphatidylinositol 3-Kinases - antagonists &amp; inhibitors</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>RNA Interference</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Surgery</subject><subject>Tumors</subject><issn>0022-4804</issn><issn>1095-8673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kk1v1DAQhi0EotvCD-CCfEGUQ8LYjuNElZBQVKBSV1R8nC3HmS1esvZiJ6v23-NlF5A4cLJGet7x-PEQ8oxByYDVr9flOqWSA7QliBJU-4AsGLSyaGolHpIFAOdF1UB1Qk5TWkOuWyUek5McEYzJZkFiZ3YYRucLRj_h7TyayflbOn1DeuV3JrngqfEDvbzbRky_yrCiSzNFd0eXOJlxDNsYJnTeJKTny-VNekWdpzfG24i5m6Wdidb5sDG0w3FMT8ijlRkTPj2eZ-Tru8sv3Yfi-uP7q-7tdWEliKkQvBlAmarvsRctMoHKGmVszVFI3siBSyPziwAa27TS1laqfmDKtGAR-kGckZeHvnm-HzOmSW9csnkC4zHMSSsh6hoqwTPJDqSNIaWIK72NbmPivWag96b1WmfTem9ag9DZdM48P3af-w0OfxK_1WbgxREwyZpxFbMQl_5yvGqUrGXmLg4cZhc7h1En69BbHFxEO-khuP-O8eaftM2f6fKF3_Ee0zrM0WfJmunENejP-5XYbwS0AEy1tfgJDVCwhA</recordid><startdate>20100301</startdate><enddate>20100301</enddate><creator>Han, Fei, Ph.D</creator><creator>Zhu, Hong-Guang, Ph.D., M.D</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20100301</creationdate><title>Caveolin-1 Regulating the Invasion and Expression of Matrix Metalloproteinase (MMPs) in Pancreatic Carcinoma Cells</title><author>Han, Fei, Ph.D ; Zhu, Hong-Guang, Ph.D., M.D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c503t-328d07a4bbeb39e13e7ca7ac62e35285d25a5002008c895c6c57bd17a90ce0bd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Biological and medical sciences</topic><topic>Carcinoma - enzymology</topic><topic>Caveolin 1 - genetics</topic><topic>Caveolin 1 - metabolism</topic><topic>caveolin-1</topic><topic>Cell Line, Tumor</topic><topic>Chromones</topic><topic>Epithelial Cells - enzymology</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Flavonoids</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gene Knockdown Techniques</topic><topic>General aspects</topic><topic>Humans</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>MAP Kinase Signaling System</topic><topic>matrix metalloproteinase</topic><topic>Matrix Metalloproteinase 2 - metabolism</topic><topic>Matrix Metalloproteinase 2 - secretion</topic><topic>Matrix Metalloproteinase 9 - metabolism</topic><topic>Matrix Metalloproteinase 9 - secretion</topic><topic>Medical sciences</topic><topic>Mitogen-Activated Protein Kinase Kinases - antagonists &amp; inhibitors</topic><topic>Morpholines</topic><topic>Neoplasm Invasiveness</topic><topic>pancreatic carcinoma</topic><topic>Pancreatic Ducts - enzymology</topic><topic>Pancreatic Neoplasms - enzymology</topic><topic>Phosphatidylinositol 3-Kinases - antagonists &amp; inhibitors</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>RNA Interference</topic><topic>RNA, Messenger - metabolism</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Surgery</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Han, Fei, Ph.D</creatorcontrib><creatorcontrib>Zhu, Hong-Guang, Ph.D., M.D</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of surgical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Han, Fei, Ph.D</au><au>Zhu, Hong-Guang, Ph.D., M.D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Caveolin-1 Regulating the Invasion and Expression of Matrix Metalloproteinase (MMPs) in Pancreatic Carcinoma Cells</atitle><jtitle>The Journal of surgical research</jtitle><addtitle>J Surg Res</addtitle><date>2010-03-01</date><risdate>2010</risdate><volume>159</volume><issue>1</issue><spage>443</spage><epage>450</epage><pages>443-450</pages><issn>0022-4804</issn><eissn>1095-8673</eissn><coden>JSGRA2</coden><abstract>The gelatinases B (MMP9) and A (MMP2) are two members of the matrix metalloproteinase (MMPs) family that are expressed in human cancer, and play a critical role in tumor cell invasion and metastasis. Caveolin-1 (Cav1) has recently been identified as a tumor metastasis modifier gene. However, the effect and mechanism of Cav1 in pancreatic carcinoma cell invasion remain unknown. In this study, we investigated the expression of Cav1, MMP2, and MMP9 in several different pancreatic carcinoma cell lines. We transfected pcDNA3.0-Cav1 plasmid and Cav1 siRNA into SW1990 and Bxpc3 cells, respectively. Using cell invasion assay, we found that overexpression of Cav1 inhibited cell invasion, whereas the knockdown of Cav1 in Bxpc3 cells promoted cell invasion. Moreover, to explore the mechanisms underlying these observations, we further investigated the expression of MMP2, MMP9, phospho-Akt, and phospho-Erk by Western blot, and the activities of MMP2 and MMP9 by gelatin zymography. The results indicated that Cav1 gene could inhibit pancreatic carcinoma cell invasion, at least in part, probably through Erk-MMP signal pathway, suggesting that the endogenous expression or re-expression of Cav1 might help therapeutically reduce their invasive potential in pancreatic carcinoma cells.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>20031158</pmid><doi>10.1016/j.jss.2009.03.079</doi><tpages>8</tpages></addata></record>
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subjects Biological and medical sciences
Carcinoma - enzymology
Caveolin 1 - genetics
Caveolin 1 - metabolism
caveolin-1
Cell Line, Tumor
Chromones
Epithelial Cells - enzymology
Extracellular Signal-Regulated MAP Kinases - metabolism
Flavonoids
Gastroenterology. Liver. Pancreas. Abdomen
Gene Knockdown Techniques
General aspects
Humans
Liver. Biliary tract. Portal circulation. Exocrine pancreas
MAP Kinase Signaling System
matrix metalloproteinase
Matrix Metalloproteinase 2 - metabolism
Matrix Metalloproteinase 2 - secretion
Matrix Metalloproteinase 9 - metabolism
Matrix Metalloproteinase 9 - secretion
Medical sciences
Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors
Morpholines
Neoplasm Invasiveness
pancreatic carcinoma
Pancreatic Ducts - enzymology
Pancreatic Neoplasms - enzymology
Phosphatidylinositol 3-Kinases - antagonists & inhibitors
Proto-Oncogene Proteins c-akt - metabolism
RNA Interference
RNA, Messenger - metabolism
RNA, Small Interfering - metabolism
Surgery
Tumors
title Caveolin-1 Regulating the Invasion and Expression of Matrix Metalloproteinase (MMPs) in Pancreatic Carcinoma Cells
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