Annexin A2 promotes the migration and invasion of human hepatocellular carcinoma cells in vitro by regulating the shedding of CD147-harboring microvesicles from tumor cells
It has been reported that Annexin A2 (ANXA2) is up-regulated in hepatocellular carcinoma (HCC), but the roles of ANXA2 in the migration and invasion of HCC cells have not been determined. In this study, we found that ANXA2-specific siRNA (si-ANXA2) significantly inhibited the migration and invasion...
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description | It has been reported that Annexin A2 (ANXA2) is up-regulated in hepatocellular carcinoma (HCC), but the roles of ANXA2 in the migration and invasion of HCC cells have not been determined. In this study, we found that ANXA2-specific siRNA (si-ANXA2) significantly inhibited the migration and invasion of HCC cells co-cultured with fibroblasts in vitro. In addition, the production of MMP-2 by fibroblasts cultured in supernatant collected from si-ANXA2-transfected HCC cells was notably down-regulated. ANXA2 was also found to be co-localized and co-immunoprecipitated with CD147. Further investigation revealed that the expression of ANXA2 in HCC cells affected the shedding of CD147-harboring membrane microvesicles, acting as a vehicle for CD147 in tumor-stromal interactions and thereby regulating the production of MMP-2 by fibroblasts. Together, these results suggest that ANXA2 enhances the migration and invasion potential of HCC cells in vitro by regulating the trafficking of CD147-harboring membrane microvesicles. |
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In this study, we found that ANXA2-specific siRNA (si-ANXA2) significantly inhibited the migration and invasion of HCC cells co-cultured with fibroblasts in vitro. In addition, the production of MMP-2 by fibroblasts cultured in supernatant collected from si-ANXA2-transfected HCC cells was notably down-regulated. ANXA2 was also found to be co-localized and co-immunoprecipitated with CD147. Further investigation revealed that the expression of ANXA2 in HCC cells affected the shedding of CD147-harboring membrane microvesicles, acting as a vehicle for CD147 in tumor-stromal interactions and thereby regulating the production of MMP-2 by fibroblasts. Together, these results suggest that ANXA2 enhances the migration and invasion potential of HCC cells in vitro by regulating the trafficking of CD147-harboring membrane microvesicles.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0067268</identifier><identifier>PMID: 23950866</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Angiogenesis ; Annexin A2 - genetics ; Annexin A2 - metabolism ; Annexins ; Basigin - metabolism ; Binding sites ; Biology ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - metabolism ; Carcinoma, Hepatocellular - pathology ; CD147 antigen ; Cell Line, Tumor ; Cell Membrane - metabolism ; Cell Movement - genetics ; Chemistry ; Coculture Techniques ; Engineering research ; Extracellular matrix ; Fibroblasts ; Gelatinase A ; Gene Expression Regulation, Neoplastic ; Hepatocellular carcinoma ; Humans ; Immunoglobulins ; Kinases ; Laboratories ; Liver cancer ; Liver Neoplasms - genetics ; Liver Neoplasms - metabolism ; Liver Neoplasms - pathology ; Medicine ; Membrane trafficking ; Metastasis ; Microvessels - metabolism ; Microvessels - pathology ; Neoplasm Invasiveness ; Neovascularization, Pathologic - genetics ; Neovascularization, Pathologic - metabolism ; Prostate cancer ; Protein Binding ; Protein Transport ; Proteins ; RNA Interference ; Shedding ; Signal transduction ; siRNA ; Surgery ; Tumor cells ; Tumors</subject><ispartof>PloS one, 2013-08, Vol.8 (8), p.e67268-e67268</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Zhang et al 2013 Zhang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-23563103a3ab083da5613aeee491d44bcb196a0b6449b8b6642aa988bef9e4013</citedby><cites>FETCH-LOGICAL-c692t-23563103a3ab083da5613aeee491d44bcb196a0b6449b8b6642aa988bef9e4013</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741296/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741296/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23950866$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Lee, Jung Weon</contributor><creatorcontrib>Zhang, Wei</creatorcontrib><creatorcontrib>Zhao, Pu</creatorcontrib><creatorcontrib>Xu, Xiu-Li</creatorcontrib><creatorcontrib>Cai, Lei</creatorcontrib><creatorcontrib>Song, Zhen-Shun</creatorcontrib><creatorcontrib>Cao, Da-Yong</creatorcontrib><creatorcontrib>Tao, Kai-Shan</creatorcontrib><creatorcontrib>Zhou, Wen-Ping</creatorcontrib><creatorcontrib>Chen, Zhi-Nan</creatorcontrib><creatorcontrib>Dou, Ke-Feng</creatorcontrib><title>Annexin A2 promotes the migration and invasion of human hepatocellular carcinoma cells in vitro by regulating the shedding of CD147-harboring microvesicles from tumor cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>It has been reported that Annexin A2 (ANXA2) is up-regulated in hepatocellular carcinoma (HCC), but the roles of ANXA2 in the migration and invasion of HCC cells have not been determined. 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Together, these results suggest that ANXA2 enhances the migration and invasion potential of HCC cells in vitro by regulating the trafficking of CD147-harboring membrane microvesicles.</description><subject>Angiogenesis</subject><subject>Annexin A2 - genetics</subject><subject>Annexin A2 - metabolism</subject><subject>Annexins</subject><subject>Basigin - metabolism</subject><subject>Binding sites</subject><subject>Biology</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>CD147 antigen</subject><subject>Cell Line, Tumor</subject><subject>Cell Membrane - metabolism</subject><subject>Cell Movement - genetics</subject><subject>Chemistry</subject><subject>Coculture Techniques</subject><subject>Engineering research</subject><subject>Extracellular matrix</subject><subject>Fibroblasts</subject><subject>Gelatinase A</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Hepatocellular carcinoma</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - pathology</subject><subject>Medicine</subject><subject>Membrane trafficking</subject><subject>Metastasis</subject><subject>Microvessels - metabolism</subject><subject>Microvessels - pathology</subject><subject>Neoplasm Invasiveness</subject><subject>Neovascularization, Pathologic - genetics</subject><subject>Neovascularization, Pathologic - metabolism</subject><subject>Prostate cancer</subject><subject>Protein Binding</subject><subject>Protein Transport</subject><subject>Proteins</subject><subject>RNA Interference</subject><subject>Shedding</subject><subject>Signal transduction</subject><subject>siRNA</subject><subject>Surgery</subject><subject>Tumor cells</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNU9tq3DAQNaWladP-QWkFhdI-7Fa3le2XwpLeAoFAb69ibI9tBVvaSvKS_FM_snJ2E7IlD8UPksbnHM0czWTZC0aXTOTs_YWbvIVhuXEWl5SqnKviQfaElYIvFKfi4Z39UfY0hAtKV6JQ6nF2xEW5omn7JPuzthYvjSVrTjbejS5iILFHMprOQzTOErANMXYLYT64lvTTCJb0uIHoahyGaQBPavC1sW4EModCIpCtid6R6op47BImGttdK4cem2Y-JK2Tj0zmix585fwcGk3t3RaDqYeUR5sSInEand-pPssetTAEfL5fj7Ofnz_9OPm6ODv_cnqyPlvUquRxwcVKCUYFCKhoIRpYKSYAEWXJGimrumKlAlopKcuqqJSSHKAsigrbEiVl4jh7tdPdDC7ovdFBMymo5FQpkRCnO0Tj4EJvvBnBX2kHRl8HnO80-DhXoWXF68QoFJZcqqKp6nrVtEKuaA4M2yJpfdjfNlUjNjXa6GE4ED38Y02vO7fVIpeMlyoJvN0LePd7whD1aMJsGFh005w3V5TlPLXDcfb6H-j91e1RHaQCjG1dureeRfVa5kXytmSzS8t7UOlrMD1j6srWpPgB4d0BIWEiXsYOphD06fdv_489_3WIfXMH2yMMsQ9umObuDYdAuQOmJgvBY3trMqN6HqobN_Q8VHo_VIn28u4D3ZJupkj8BQuaHrI</recordid><startdate>20130812</startdate><enddate>20130812</enddate><creator>Zhang, Wei</creator><creator>Zhao, Pu</creator><creator>Xu, Xiu-Li</creator><creator>Cai, Lei</creator><creator>Song, Zhen-Shun</creator><creator>Cao, Da-Yong</creator><creator>Tao, Kai-Shan</creator><creator>Zhou, Wen-Ping</creator><creator>Chen, Zhi-Nan</creator><creator>Dou, Ke-Feng</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130812</creationdate><title>Annexin A2 promotes the migration and invasion of human hepatocellular carcinoma cells in vitro by regulating the shedding of CD147-harboring microvesicles from tumor cells</title><author>Zhang, Wei ; Zhao, Pu ; Xu, Xiu-Li ; Cai, Lei ; Song, Zhen-Shun ; Cao, Da-Yong ; Tao, Kai-Shan ; Zhou, Wen-Ping ; Chen, Zhi-Nan ; Dou, Ke-Feng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-23563103a3ab083da5613aeee491d44bcb196a0b6449b8b6642aa988bef9e4013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Angiogenesis</topic><topic>Annexin A2 - genetics</topic><topic>Annexin A2 - metabolism</topic><topic>Annexins</topic><topic>Basigin - metabolism</topic><topic>Binding sites</topic><topic>Biology</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>CD147 antigen</topic><topic>Cell Line, Tumor</topic><topic>Cell Membrane - metabolism</topic><topic>Cell Movement - genetics</topic><topic>Chemistry</topic><topic>Coculture Techniques</topic><topic>Engineering research</topic><topic>Extracellular matrix</topic><topic>Fibroblasts</topic><topic>Gelatinase A</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Hepatocellular carcinoma</topic><topic>Humans</topic><topic>Immunoglobulins</topic><topic>Kinases</topic><topic>Laboratories</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - pathology</topic><topic>Medicine</topic><topic>Membrane trafficking</topic><topic>Metastasis</topic><topic>Microvessels - metabolism</topic><topic>Microvessels - pathology</topic><topic>Neoplasm Invasiveness</topic><topic>Neovascularization, Pathologic - genetics</topic><topic>Neovascularization, Pathologic - metabolism</topic><topic>Prostate cancer</topic><topic>Protein Binding</topic><topic>Protein Transport</topic><topic>Proteins</topic><topic>RNA Interference</topic><topic>Shedding</topic><topic>Signal transduction</topic><topic>siRNA</topic><topic>Surgery</topic><topic>Tumor cells</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Wei</creatorcontrib><creatorcontrib>Zhao, Pu</creatorcontrib><creatorcontrib>Xu, Xiu-Li</creatorcontrib><creatorcontrib>Cai, Lei</creatorcontrib><creatorcontrib>Song, Zhen-Shun</creatorcontrib><creatorcontrib>Cao, Da-Yong</creatorcontrib><creatorcontrib>Tao, Kai-Shan</creatorcontrib><creatorcontrib>Zhou, Wen-Ping</creatorcontrib><creatorcontrib>Chen, Zhi-Nan</creatorcontrib><creatorcontrib>Dou, Ke-Feng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale in Context : Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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In this study, we found that ANXA2-specific siRNA (si-ANXA2) significantly inhibited the migration and invasion of HCC cells co-cultured with fibroblasts in vitro. In addition, the production of MMP-2 by fibroblasts cultured in supernatant collected from si-ANXA2-transfected HCC cells was notably down-regulated. ANXA2 was also found to be co-localized and co-immunoprecipitated with CD147. Further investigation revealed that the expression of ANXA2 in HCC cells affected the shedding of CD147-harboring membrane microvesicles, acting as a vehicle for CD147 in tumor-stromal interactions and thereby regulating the production of MMP-2 by fibroblasts. Together, these results suggest that ANXA2 enhances the migration and invasion potential of HCC cells in vitro by regulating the trafficking of CD147-harboring membrane microvesicles.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23950866</pmid><doi>10.1371/journal.pone.0067268</doi><tpages>e67268</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Angiogenesis Annexin A2 - genetics Annexin A2 - metabolism Annexins Basigin - metabolism Binding sites Biology Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - pathology CD147 antigen Cell Line, Tumor Cell Membrane - metabolism Cell Movement - genetics Chemistry Coculture Techniques Engineering research Extracellular matrix Fibroblasts Gelatinase A Gene Expression Regulation, Neoplastic Hepatocellular carcinoma Humans Immunoglobulins Kinases Laboratories Liver cancer Liver Neoplasms - genetics Liver Neoplasms - metabolism Liver Neoplasms - pathology Medicine Membrane trafficking Metastasis Microvessels - metabolism Microvessels - pathology Neoplasm Invasiveness Neovascularization, Pathologic - genetics Neovascularization, Pathologic - metabolism Prostate cancer Protein Binding Protein Transport Proteins RNA Interference Shedding Signal transduction siRNA Surgery Tumor cells Tumors |
title | Annexin A2 promotes the migration and invasion of human hepatocellular carcinoma cells in vitro by regulating the shedding of CD147-harboring microvesicles from tumor cells |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-20T20%3A43%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Annexin%20A2%20promotes%20the%20migration%20and%20invasion%20of%20human%20hepatocellular%20carcinoma%20cells%20in%20vitro%20by%20regulating%20the%20shedding%20of%20CD147-harboring%20microvesicles%20from%20tumor%20cells&rft.jtitle=PloS%20one&rft.au=Zhang,%20Wei&rft.date=2013-08-12&rft.volume=8&rft.issue=8&rft.spage=e67268&rft.epage=e67268&rft.pages=e67268-e67268&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0067268&rft_dat=%3Cgale_plos_%3EA478310911%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1430420663&rft_id=info:pmid/23950866&rft_galeid=A478310911&rft_doaj_id=oai_doaj_org_article_4b2c63386e92468dbcc5df34507a1ef8&rfr_iscdi=true |