CD90 Expression Controls Migration and Predicts Dasatinib Response in Glioblastoma
CD90 (Thy-1) is a glycophosphatidylinositol-anchored glycoprotein considered as a surrogate marker for a variety of stem cells, including glioblastoma (GBM) stem cells (GSC). However, the molecular and cellular functions of CD90 remain unclear. The function of CD90 in GBM was addressed using cellula...
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| Veröffentlicht in: | Clinical cancer research 2017-12, Vol.23 (23), p.7360-7374 |
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| creator | Avril, Tony Etcheverry, Amandine Pineau, Raphaël Obacz, Joanna Jegou, Gwénaële Jouan, Florence Le Reste, Pierre-Jean Hatami, Masumeh Colen, Rivka R Carlson, Brett L Decker, Paul A Sarkaria, Jann N Vauléon, Elodie Chiforeanu, Dan Cristian Clavreul, Anne Mosser, Jean Chevet, Eric Quillien, Véronique |
| description | CD90 (Thy-1) is a glycophosphatidylinositol-anchored glycoprotein considered as a surrogate marker for a variety of stem cells, including glioblastoma (GBM) stem cells (GSC). However, the molecular and cellular functions of CD90 remain unclear.
The function of CD90 in GBM was addressed using cellular models from immortalized and primary GBM lines,
orthotopic mouse models, and GBM specimens' transcriptome associated with MRI features from GBM patients. CD90 expression was silenced in U251 and GBM primary cells and complemented in CD90-negative U87 cells.
We showed that CD90 is not only expressed on GSCs but also on more differentiated GBM cancer cells. In GBM patients, CD90 expression was associated with an adhesion/migration gene signature and with invasive tumor features. Modulation of CD90 expression in GBM cells dramatically affected their adhesion and migration properties. Moreover, orthotopic xenografts revealed that CD90 expression induced invasive phenotypes
Indeed, CD90 expression led to enhanced SRC and FAK signaling in our GBM cellular models and GBM patients' specimens. Pharmacologic inhibition of these signaling nodes blunted adhesion and migration in CD90-positive cells. Remarkably, dasatinib blunted CD90-dependent GBM cell invasion
and killed CD90
primary GSC lines.
Our data demonstrate that CD90 is an actor of GBM invasiveness through SRC-dependent mechanisms and could be used as a predictive factor for dasatinib response in CD90
GBM patients.
. |
| doi_str_mv | 10.1158/1078-0432.CCR-17-1549 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_01671761v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1942704134</sourcerecordid><originalsourceid>FETCH-LOGICAL-c470t-40e9704b54a6d0e42a419bea27b1a286a59cee3ca7bae06636323ea4a2740a03</originalsourceid><addsrcrecordid>eNpdkU1LxDAQhoMofqz-BKXgRQ_VTJI2zVHqJ6woi_cw7Y4a6TZr0hX996asevA0w8szwzvzMnYI_AygqM6B6yrnSoqzup7loHMolNlgu1AUOpeiLDZT_8vssL0Y3zgHBVxtsx1RGWm0MrtsVl8anl19LgPF6Hyf1b4fgu9idu9eAg6jhP08eww0d-0Qs0uMSe1dk80oLn0fKXN9dtM533QYB7_Afbb1jF2kg586YU_XV0_1bT59uLmrL6Z5qzQfcsXJaK6aQmE556QEKjANodANoKhKLExLJFvUDRIvS1lKIQlVAhRHLifsdL32FTu7DG6B4ct6dPb2YmpHjUOpQZfwAYk9WbPL4N9XFAe7cLGlrsOe_CpaMEokLyBVQo__oW9-Ffp0SKIqqQRUycmEFWuqDT7GQM9_DoDbMR87_t6Ov7cpHwvajvmkuaOf7atmQfO_qd9A5DeAuYlX</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1983421836</pqid></control><display><type>article</type><title>CD90 Expression Controls Migration and Predicts Dasatinib Response in Glioblastoma</title><source>American Association for Cancer Research</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Avril, Tony ; Etcheverry, Amandine ; Pineau, Raphaël ; Obacz, Joanna ; Jegou, Gwénaële ; Jouan, Florence ; Le Reste, Pierre-Jean ; Hatami, Masumeh ; Colen, Rivka R ; Carlson, Brett L ; Decker, Paul A ; Sarkaria, Jann N ; Vauléon, Elodie ; Chiforeanu, Dan Cristian ; Clavreul, Anne ; Mosser, Jean ; Chevet, Eric ; Quillien, Véronique</creator><creatorcontrib>Avril, Tony ; Etcheverry, Amandine ; Pineau, Raphaël ; Obacz, Joanna ; Jegou, Gwénaële ; Jouan, Florence ; Le Reste, Pierre-Jean ; Hatami, Masumeh ; Colen, Rivka R ; Carlson, Brett L ; Decker, Paul A ; Sarkaria, Jann N ; Vauléon, Elodie ; Chiforeanu, Dan Cristian ; Clavreul, Anne ; Mosser, Jean ; Chevet, Eric ; Quillien, Véronique</creatorcontrib><description>CD90 (Thy-1) is a glycophosphatidylinositol-anchored glycoprotein considered as a surrogate marker for a variety of stem cells, including glioblastoma (GBM) stem cells (GSC). However, the molecular and cellular functions of CD90 remain unclear.
The function of CD90 in GBM was addressed using cellular models from immortalized and primary GBM lines,
orthotopic mouse models, and GBM specimens' transcriptome associated with MRI features from GBM patients. CD90 expression was silenced in U251 and GBM primary cells and complemented in CD90-negative U87 cells.
We showed that CD90 is not only expressed on GSCs but also on more differentiated GBM cancer cells. In GBM patients, CD90 expression was associated with an adhesion/migration gene signature and with invasive tumor features. Modulation of CD90 expression in GBM cells dramatically affected their adhesion and migration properties. Moreover, orthotopic xenografts revealed that CD90 expression induced invasive phenotypes
Indeed, CD90 expression led to enhanced SRC and FAK signaling in our GBM cellular models and GBM patients' specimens. Pharmacologic inhibition of these signaling nodes blunted adhesion and migration in CD90-positive cells. Remarkably, dasatinib blunted CD90-dependent GBM cell invasion
and killed CD90
primary GSC lines.
Our data demonstrate that CD90 is an actor of GBM invasiveness through SRC-dependent mechanisms and could be used as a predictive factor for dasatinib response in CD90
GBM patients.
.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-17-1549</identifier><identifier>PMID: 28939749</identifier><language>eng</language><publisher>United States: American Association for Cancer Research Inc</publisher><subject>Adhesion ; Animal models ; Cancer ; CD90 antigen ; Cell migration ; Experimental design ; Gene expression ; Glioblastoma ; Glycoproteins ; Invasiveness ; Life Sciences ; Magnetic resonance imaging ; Mathematical models ; Neurobiology ; Neurons and Cognition ; Patients ; Pharmaceutical sciences ; Pharmacology ; Signaling ; Stem cell transplantation ; Stem cells ; Xenografts</subject><ispartof>Clinical cancer research, 2017-12, Vol.23 (23), p.7360-7374</ispartof><rights>2017 American Association for Cancer Research.</rights><rights>Copyright American Association for Cancer Research Inc Dec 1, 2017</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-40e9704b54a6d0e42a419bea27b1a286a59cee3ca7bae06636323ea4a2740a03</citedby><cites>FETCH-LOGICAL-c470t-40e9704b54a6d0e42a419bea27b1a286a59cee3ca7bae06636323ea4a2740a03</cites><orcidid>0000-0001-9019-9778 ; 0000-0001-5855-4522 ; 0000-0002-1129-8514 ; 0000-0003-4092-8308 ; 0000-0002-4477-8282</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,3343,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28939749$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://univ-rennes.hal.science/hal-01671761$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Avril, Tony</creatorcontrib><creatorcontrib>Etcheverry, Amandine</creatorcontrib><creatorcontrib>Pineau, Raphaël</creatorcontrib><creatorcontrib>Obacz, Joanna</creatorcontrib><creatorcontrib>Jegou, Gwénaële</creatorcontrib><creatorcontrib>Jouan, Florence</creatorcontrib><creatorcontrib>Le Reste, Pierre-Jean</creatorcontrib><creatorcontrib>Hatami, Masumeh</creatorcontrib><creatorcontrib>Colen, Rivka R</creatorcontrib><creatorcontrib>Carlson, Brett L</creatorcontrib><creatorcontrib>Decker, Paul A</creatorcontrib><creatorcontrib>Sarkaria, Jann N</creatorcontrib><creatorcontrib>Vauléon, Elodie</creatorcontrib><creatorcontrib>Chiforeanu, Dan Cristian</creatorcontrib><creatorcontrib>Clavreul, Anne</creatorcontrib><creatorcontrib>Mosser, Jean</creatorcontrib><creatorcontrib>Chevet, Eric</creatorcontrib><creatorcontrib>Quillien, Véronique</creatorcontrib><title>CD90 Expression Controls Migration and Predicts Dasatinib Response in Glioblastoma</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>CD90 (Thy-1) is a glycophosphatidylinositol-anchored glycoprotein considered as a surrogate marker for a variety of stem cells, including glioblastoma (GBM) stem cells (GSC). However, the molecular and cellular functions of CD90 remain unclear.
The function of CD90 in GBM was addressed using cellular models from immortalized and primary GBM lines,
orthotopic mouse models, and GBM specimens' transcriptome associated with MRI features from GBM patients. CD90 expression was silenced in U251 and GBM primary cells and complemented in CD90-negative U87 cells.
We showed that CD90 is not only expressed on GSCs but also on more differentiated GBM cancer cells. In GBM patients, CD90 expression was associated with an adhesion/migration gene signature and with invasive tumor features. Modulation of CD90 expression in GBM cells dramatically affected their adhesion and migration properties. Moreover, orthotopic xenografts revealed that CD90 expression induced invasive phenotypes
Indeed, CD90 expression led to enhanced SRC and FAK signaling in our GBM cellular models and GBM patients' specimens. Pharmacologic inhibition of these signaling nodes blunted adhesion and migration in CD90-positive cells. Remarkably, dasatinib blunted CD90-dependent GBM cell invasion
and killed CD90
primary GSC lines.
Our data demonstrate that CD90 is an actor of GBM invasiveness through SRC-dependent mechanisms and could be used as a predictive factor for dasatinib response in CD90
GBM patients.
.</description><subject>Adhesion</subject><subject>Animal models</subject><subject>Cancer</subject><subject>CD90 antigen</subject><subject>Cell migration</subject><subject>Experimental design</subject><subject>Gene expression</subject><subject>Glioblastoma</subject><subject>Glycoproteins</subject><subject>Invasiveness</subject><subject>Life Sciences</subject><subject>Magnetic resonance imaging</subject><subject>Mathematical models</subject><subject>Neurobiology</subject><subject>Neurons and Cognition</subject><subject>Patients</subject><subject>Pharmaceutical sciences</subject><subject>Pharmacology</subject><subject>Signaling</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Xenografts</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNpdkU1LxDAQhoMofqz-BKXgRQ_VTJI2zVHqJ6woi_cw7Y4a6TZr0hX996asevA0w8szwzvzMnYI_AygqM6B6yrnSoqzup7loHMolNlgu1AUOpeiLDZT_8vssL0Y3zgHBVxtsx1RGWm0MrtsVl8anl19LgPF6Hyf1b4fgu9idu9eAg6jhP08eww0d-0Qs0uMSe1dk80oLn0fKXN9dtM533QYB7_Afbb1jF2kg586YU_XV0_1bT59uLmrL6Z5qzQfcsXJaK6aQmE556QEKjANodANoKhKLExLJFvUDRIvS1lKIQlVAhRHLifsdL32FTu7DG6B4ct6dPb2YmpHjUOpQZfwAYk9WbPL4N9XFAe7cLGlrsOe_CpaMEokLyBVQo__oW9-Ffp0SKIqqQRUycmEFWuqDT7GQM9_DoDbMR87_t6Ov7cpHwvajvmkuaOf7atmQfO_qd9A5DeAuYlX</recordid><startdate>20171201</startdate><enddate>20171201</enddate><creator>Avril, Tony</creator><creator>Etcheverry, Amandine</creator><creator>Pineau, Raphaël</creator><creator>Obacz, Joanna</creator><creator>Jegou, Gwénaële</creator><creator>Jouan, Florence</creator><creator>Le Reste, Pierre-Jean</creator><creator>Hatami, Masumeh</creator><creator>Colen, Rivka R</creator><creator>Carlson, Brett L</creator><creator>Decker, Paul A</creator><creator>Sarkaria, Jann N</creator><creator>Vauléon, Elodie</creator><creator>Chiforeanu, Dan Cristian</creator><creator>Clavreul, Anne</creator><creator>Mosser, Jean</creator><creator>Chevet, Eric</creator><creator>Quillien, Véronique</creator><general>American Association for Cancer Research Inc</general><general>American Association for Cancer Research</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7T5</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><orcidid>https://orcid.org/0000-0001-9019-9778</orcidid><orcidid>https://orcid.org/0000-0001-5855-4522</orcidid><orcidid>https://orcid.org/0000-0002-1129-8514</orcidid><orcidid>https://orcid.org/0000-0003-4092-8308</orcidid><orcidid>https://orcid.org/0000-0002-4477-8282</orcidid></search><sort><creationdate>20171201</creationdate><title>CD90 Expression Controls Migration and Predicts Dasatinib Response in Glioblastoma</title><author>Avril, Tony ; 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However, the molecular and cellular functions of CD90 remain unclear.
The function of CD90 in GBM was addressed using cellular models from immortalized and primary GBM lines,
orthotopic mouse models, and GBM specimens' transcriptome associated with MRI features from GBM patients. CD90 expression was silenced in U251 and GBM primary cells and complemented in CD90-negative U87 cells.
We showed that CD90 is not only expressed on GSCs but also on more differentiated GBM cancer cells. In GBM patients, CD90 expression was associated with an adhesion/migration gene signature and with invasive tumor features. Modulation of CD90 expression in GBM cells dramatically affected their adhesion and migration properties. Moreover, orthotopic xenografts revealed that CD90 expression induced invasive phenotypes
Indeed, CD90 expression led to enhanced SRC and FAK signaling in our GBM cellular models and GBM patients' specimens. Pharmacologic inhibition of these signaling nodes blunted adhesion and migration in CD90-positive cells. Remarkably, dasatinib blunted CD90-dependent GBM cell invasion
and killed CD90
primary GSC lines.
Our data demonstrate that CD90 is an actor of GBM invasiveness through SRC-dependent mechanisms and could be used as a predictive factor for dasatinib response in CD90
GBM patients.
.</abstract><cop>United States</cop><pub>American Association for Cancer Research Inc</pub><pmid>28939749</pmid><doi>10.1158/1078-0432.CCR-17-1549</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0001-9019-9778</orcidid><orcidid>https://orcid.org/0000-0001-5855-4522</orcidid><orcidid>https://orcid.org/0000-0002-1129-8514</orcidid><orcidid>https://orcid.org/0000-0003-4092-8308</orcidid><orcidid>https://orcid.org/0000-0002-4477-8282</orcidid><oa>free_for_read</oa></addata></record> |
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| source | American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adhesion Animal models Cancer CD90 antigen Cell migration Experimental design Gene expression Glioblastoma Glycoproteins Invasiveness Life Sciences Magnetic resonance imaging Mathematical models Neurobiology Neurons and Cognition Patients Pharmaceutical sciences Pharmacology Signaling Stem cell transplantation Stem cells Xenografts |
| title | CD90 Expression Controls Migration and Predicts Dasatinib Response in Glioblastoma |
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