Fibronectin expression in glioblastomas promotes cell cohesion, collective invasion of basement membrane in vitro and orthotopic tumor growth in mice
Glioblastoma multiforme (GBM) are highly invasive and angiogenic malignancies with a median survival time from diagnosis of
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| Veröffentlicht in: | Oncogene 2014-06, Vol.33 (26), p.3451-3462 |
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| container_title | Oncogene |
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| creator | Serres, E Debarbieux, F Stanchi, F Maggiorella, L Grall, D Turchi, L Burel-Vandenbos, F Figarella-Branger, D Virolle, T Rougon, G Van Obberghen-Schilling, E |
| description | Glioblastoma multiforme (GBM) are highly invasive and angiogenic malignancies with a median survival time from diagnosis of |
| doi_str_mv | 10.1038/onc.2013.305 |
| format | Article |
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Previous work has revealed robust overexpression of fibronectin (FN) mRNA in GBM, although immunohistochemical staining of FN in these tumors is typically associated with the angiogenic vasculature. Here we sought to examine the expression of tumor cell FN and address its possible involvement in the invasive phenotype of GBM. We found that FN was expressed and assembled into fibrillar arrays in human tumors and in established GBM lines. Cultured cells spontaneously formed dense cellular networks and spheroid-like domes. Depletion of FN by targeted-short hairpin RNA expression disrupted matrix assembly and multicellular network organization by exerting profound effects on cell adhesion and motility. Although FN depletion enhanced persistent directional migration of single cells, it compromised collective invasion of spheroids through a laminin-rich matrix and sensitized cells to ionizing radiation. In orthotopic grafts, FN depletion significantly reduced tumor growth and angiogenesis. Together our results show that FN produced by the tumor cells has a role in GBM pathophysiology and they provide insights into the implications that targeting FN interactions may have for combating this dreaded disease.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/onc.2013.305</identifier><identifier>PMID: 23912459</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67/1922 ; 631/80/79/1236 ; 631/80/84/2336 ; Angiogenesis ; Animals ; Apoptosis ; Basement Membrane - cytology ; Basement membranes ; Brain cancer ; Cancer ; Care and treatment ; Cell adhesion ; Cell Adhesion - genetics ; Cell Biology ; Cell migration ; Cell Movement - genetics ; Cell Proliferation ; Cell Survival - genetics ; Cellular Biology ; Development and progression ; Extracellular Matrix ; Fibronectin ; Fibronectins ; Fibronectins - biosynthesis ; Fibronectins - genetics ; Fibronectins - metabolism ; Gene Expression Regulation, Neoplastic ; Genetic aspects ; Glioblastoma ; Glioblastoma - metabolism ; Glioblastoma - mortality ; Glioblastoma - pathology ; Glioblastoma multiforme ; Glioma ; Growth ; Human Genetics ; Humans ; Identification and classification ; Immunohistochemistry ; Integrin alpha5beta1 - metabolism ; Internal Medicine ; Ionizing radiation ; Laminin ; Life Sciences ; Medicine ; Medicine & Public Health ; Messenger RNA ; Mice ; mRNA ; Neoplasm Invasiveness ; Neovascularization, Pathologic - genetics ; Oncology ; Oncology, Experimental ; original-article ; Phenotypes ; Protein Isoforms - biosynthesis ; Protein Isoforms - genetics ; RNA Interference ; RNA, Small Interfering ; Spheroids ; Spheroids, Cellular ; Tumor cells ; Tumor Cells, Cultured ; Tumors</subject><ispartof>Oncogene, 2014-06, Vol.33 (26), p.3451-3462</ispartof><rights>Macmillan Publishers Limited 2014</rights><rights>COPYRIGHT 2014 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jun 26, 2014</rights><rights>Macmillan Publishers Limited 2014.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c622t-253608b057a051e834efed342c59f7c483fef63c5d3a207feaefbacfaf0fae03</citedby><cites>FETCH-LOGICAL-c622t-253608b057a051e834efed342c59f7c483fef63c5d3a207feaefbacfaf0fae03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/onc.2013.305$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/onc.2013.305$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23912459$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-00862133$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Serres, E</creatorcontrib><creatorcontrib>Debarbieux, F</creatorcontrib><creatorcontrib>Stanchi, F</creatorcontrib><creatorcontrib>Maggiorella, L</creatorcontrib><creatorcontrib>Grall, D</creatorcontrib><creatorcontrib>Turchi, L</creatorcontrib><creatorcontrib>Burel-Vandenbos, F</creatorcontrib><creatorcontrib>Figarella-Branger, D</creatorcontrib><creatorcontrib>Virolle, T</creatorcontrib><creatorcontrib>Rougon, G</creatorcontrib><creatorcontrib>Van Obberghen-Schilling, E</creatorcontrib><title>Fibronectin expression in glioblastomas promotes cell cohesion, collective invasion of basement membrane in vitro and orthotopic tumor growth in mice</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Glioblastoma multiforme (GBM) are highly invasive and angiogenic malignancies with a median survival time from diagnosis of <15 months. Previous work has revealed robust overexpression of fibronectin (FN) mRNA in GBM, although immunohistochemical staining of FN in these tumors is typically associated with the angiogenic vasculature. Here we sought to examine the expression of tumor cell FN and address its possible involvement in the invasive phenotype of GBM. We found that FN was expressed and assembled into fibrillar arrays in human tumors and in established GBM lines. Cultured cells spontaneously formed dense cellular networks and spheroid-like domes. Depletion of FN by targeted-short hairpin RNA expression disrupted matrix assembly and multicellular network organization by exerting profound effects on cell adhesion and motility. Although FN depletion enhanced persistent directional migration of single cells, it compromised collective invasion of spheroids through a laminin-rich matrix and sensitized cells to ionizing radiation. In orthotopic grafts, FN depletion significantly reduced tumor growth and angiogenesis. Together our results show that FN produced by the tumor cells has a role in GBM pathophysiology and they provide insights into the implications that targeting FN interactions may have for combating this dreaded disease.</description><subject>631/67/1922</subject><subject>631/80/79/1236</subject><subject>631/80/84/2336</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Basement Membrane - cytology</subject><subject>Basement membranes</subject><subject>Brain cancer</subject><subject>Cancer</subject><subject>Care and treatment</subject><subject>Cell adhesion</subject><subject>Cell Adhesion - genetics</subject><subject>Cell Biology</subject><subject>Cell migration</subject><subject>Cell Movement - genetics</subject><subject>Cell Proliferation</subject><subject>Cell Survival - genetics</subject><subject>Cellular Biology</subject><subject>Development and progression</subject><subject>Extracellular Matrix</subject><subject>Fibronectin</subject><subject>Fibronectins</subject><subject>Fibronectins - biosynthesis</subject><subject>Fibronectins - genetics</subject><subject>Fibronectins - metabolism</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genetic aspects</subject><subject>Glioblastoma</subject><subject>Glioblastoma - metabolism</subject><subject>Glioblastoma - mortality</subject><subject>Glioblastoma - pathology</subject><subject>Glioblastoma multiforme</subject><subject>Glioma</subject><subject>Growth</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Identification and classification</subject><subject>Immunohistochemistry</subject><subject>Integrin alpha5beta1 - metabolism</subject><subject>Internal Medicine</subject><subject>Ionizing radiation</subject><subject>Laminin</subject><subject>Life Sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Messenger RNA</subject><subject>Mice</subject><subject>mRNA</subject><subject>Neoplasm Invasiveness</subject><subject>Neovascularization, Pathologic - genetics</subject><subject>Oncology</subject><subject>Oncology, Experimental</subject><subject>original-article</subject><subject>Phenotypes</subject><subject>Protein Isoforms - biosynthesis</subject><subject>Protein Isoforms - genetics</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering</subject><subject>Spheroids</subject><subject>Spheroids, Cellular</subject><subject>Tumor cells</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkktvEzEUhS0EoiGwY40ssQGpE67t8TyWUUUpUiQ23Vsez3XiamYcbCeFH8L_xUNKVVCFkBd-fefY9-oQ8prBioFoPvjJrDgwsRIgn5AFK-uqkLItn5IFtBKKlgt-Rl7EeAMAdQv8OTnjomW8lO2C_Lh0XfATmuQmit_2AWN0fqJ5tx2c7wYdkx91pPvgR58wUoPDQI3f4cyd59UwzOojZs1R_xJ7SzsdccQp0RHHLuhpvqVHl4KneuqpD2nnk987Q9Nh9IFug79NuxkancGX5JnVQ8RXd_OSXF9-vL64KjZfPn2-WG8KU3GeCi5FBU0HstYgGTaiRIu9KLmRra1N2QiLthJG9kJzqC1qtJ02VluwGkEsyfuT7U4Pah_cqMN35bVTV-uNms8AmoozIY4ss-9ObG7E1wPGpEYX517k2vwhKialBFY3Zf0faMlEw5psvCRv_0Jv_CFMuWbFq5JJPpv-i8peUMum4Q-8tnpA5SbrU9BmflqtRV1JBkxWmVo9QuXRY-58ToJ1-fwPwflJYIKPMaC97xQDNSdQ5QSqOYEqJzDjb-7-euhG7O_h35HLQHECYr6athgeFPOY4U8L9OV7</recordid><startdate>20140626</startdate><enddate>20140626</enddate><creator>Serres, E</creator><creator>Debarbieux, F</creator><creator>Stanchi, F</creator><creator>Maggiorella, L</creator><creator>Grall, D</creator><creator>Turchi, L</creator><creator>Burel-Vandenbos, F</creator><creator>Figarella-Branger, D</creator><creator>Virolle, T</creator><creator>Rougon, G</creator><creator>Van Obberghen-Schilling, E</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><general>Nature Publishing Group [1987-....]</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>3V.</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>1XC</scope></search><sort><creationdate>20140626</creationdate><title>Fibronectin expression in glioblastomas promotes cell cohesion, collective invasion of basement membrane in vitro and orthotopic tumor growth in mice</title><author>Serres, E ; Debarbieux, F ; Stanchi, F ; Maggiorella, L ; Grall, D ; Turchi, L ; Burel-Vandenbos, F ; Figarella-Branger, D ; Virolle, T ; Rougon, G ; Van Obberghen-Schilling, E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c622t-253608b057a051e834efed342c59f7c483fef63c5d3a207feaefbacfaf0fae03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>631/67/1922</topic><topic>631/80/79/1236</topic><topic>631/80/84/2336</topic><topic>Angiogenesis</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Basement Membrane - cytology</topic><topic>Basement membranes</topic><topic>Brain cancer</topic><topic>Cancer</topic><topic>Care and treatment</topic><topic>Cell adhesion</topic><topic>Cell Adhesion - genetics</topic><topic>Cell Biology</topic><topic>Cell migration</topic><topic>Cell Movement - genetics</topic><topic>Cell Proliferation</topic><topic>Cell Survival - genetics</topic><topic>Cellular Biology</topic><topic>Development and progression</topic><topic>Extracellular Matrix</topic><topic>Fibronectin</topic><topic>Fibronectins</topic><topic>Fibronectins - biosynthesis</topic><topic>Fibronectins - genetics</topic><topic>Fibronectins - metabolism</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genetic aspects</topic><topic>Glioblastoma</topic><topic>Glioblastoma - metabolism</topic><topic>Glioblastoma - mortality</topic><topic>Glioblastoma - pathology</topic><topic>Glioblastoma multiforme</topic><topic>Glioma</topic><topic>Growth</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Identification and classification</topic><topic>Immunohistochemistry</topic><topic>Integrin alpha5beta1 - 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Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Serres, E</au><au>Debarbieux, F</au><au>Stanchi, F</au><au>Maggiorella, L</au><au>Grall, D</au><au>Turchi, L</au><au>Burel-Vandenbos, F</au><au>Figarella-Branger, D</au><au>Virolle, T</au><au>Rougon, G</au><au>Van Obberghen-Schilling, E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fibronectin expression in glioblastomas promotes cell cohesion, collective invasion of basement membrane in vitro and orthotopic tumor growth in mice</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2014-06-26</date><risdate>2014</risdate><volume>33</volume><issue>26</issue><spage>3451</spage><epage>3462</epage><pages>3451-3462</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>Glioblastoma multiforme (GBM) are highly invasive and angiogenic malignancies with a median survival time from diagnosis of <15 months. Previous work has revealed robust overexpression of fibronectin (FN) mRNA in GBM, although immunohistochemical staining of FN in these tumors is typically associated with the angiogenic vasculature. Here we sought to examine the expression of tumor cell FN and address its possible involvement in the invasive phenotype of GBM. We found that FN was expressed and assembled into fibrillar arrays in human tumors and in established GBM lines. Cultured cells spontaneously formed dense cellular networks and spheroid-like domes. Depletion of FN by targeted-short hairpin RNA expression disrupted matrix assembly and multicellular network organization by exerting profound effects on cell adhesion and motility. Although FN depletion enhanced persistent directional migration of single cells, it compromised collective invasion of spheroids through a laminin-rich matrix and sensitized cells to ionizing radiation. In orthotopic grafts, FN depletion significantly reduced tumor growth and angiogenesis. Together our results show that FN produced by the tumor cells has a role in GBM pathophysiology and they provide insights into the implications that targeting FN interactions may have for combating this dreaded disease.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>23912459</pmid><doi>10.1038/onc.2013.305</doi><tpages>12</tpages></addata></record> |
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| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature; EZB-FREE-00999 freely available EZB journals |
| subjects | 631/67/1922 631/80/79/1236 631/80/84/2336 Angiogenesis Animals Apoptosis Basement Membrane - cytology Basement membranes Brain cancer Cancer Care and treatment Cell adhesion Cell Adhesion - genetics Cell Biology Cell migration Cell Movement - genetics Cell Proliferation Cell Survival - genetics Cellular Biology Development and progression Extracellular Matrix Fibronectin Fibronectins Fibronectins - biosynthesis Fibronectins - genetics Fibronectins - metabolism Gene Expression Regulation, Neoplastic Genetic aspects Glioblastoma Glioblastoma - metabolism Glioblastoma - mortality Glioblastoma - pathology Glioblastoma multiforme Glioma Growth Human Genetics Humans Identification and classification Immunohistochemistry Integrin alpha5beta1 - metabolism Internal Medicine Ionizing radiation Laminin Life Sciences Medicine Medicine & Public Health Messenger RNA Mice mRNA Neoplasm Invasiveness Neovascularization, Pathologic - genetics Oncology Oncology, Experimental original-article Phenotypes Protein Isoforms - biosynthesis Protein Isoforms - genetics RNA Interference RNA, Small Interfering Spheroids Spheroids, Cellular Tumor cells Tumor Cells, Cultured Tumors |
| title | Fibronectin expression in glioblastomas promotes cell cohesion, collective invasion of basement membrane in vitro and orthotopic tumor growth in mice |
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