Tenascin-c mediated vasculogenic mimicry formation via regulation of MMP2/MMP9 in glioma
Vasculogenic mimicry (VM), the formation of vessel-like structures by highly invasive tumor cells, has been considered one of several mechanisms responsible for the failure of anti-angiogenesis therapy in glioma patients. Therefore, inhibiting VM formation might be an effective therapeutic method to...
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| Veröffentlicht in: | Cell death & disease 2019-11, Vol.10 (12), p.1-14, Article 879 |
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| creator | Cai, Hai-ping Wang, Jing Xi, Shao-yan Ni, Xiang-rong Chen, Yin-sheng Yu, Yan-jiao Cen, Zi-wen Yu, Zhi-hui Chen, Fu-rong Guo, Cheng-cheng Zhang, Ji Ke, Chao Wang, Jian Chen, Zhong-ping |
| description | Vasculogenic mimicry (VM), the formation of vessel-like structures by highly invasive tumor cells, has been considered one of several mechanisms responsible for the failure of anti-angiogenesis therapy in glioma patients. Therefore, inhibiting VM formation might be an effective therapeutic method to antagonize the angiogenesis resistance. This study aimed to show that an extracellular protein called Tenascin-c (TNC) is involved in VM formation and that TNC knockdown inhibits VM in glioma. TNC was upregulated with an increase in glioma grade. TNC and VM formation are potential independent predictors of survival of glioma patients. TNC upregulation was correlated with VM formation, and exogenous TNC stimulated VM formation. Furthermore, TNC knockdown significantly suppressed VM formation and proliferation in glioma cells in vitro and in vivo, with a reduction in cellular invasiveness and migration. Mechanistically, TNC knockdown decreased Akt phosphorylation at Ser
473
and Thr
308
and subsequently downregulated matrix metalloproteinase 2 and 9, both of which are important proteins associated with VM formation and migration. Our results indicate that TNC plays an important role in VM formation in glioma, suggesting that TNC is a potential therapeutic target for anti-angiogenesis therapy for glioma. |
| doi_str_mv | 10.1038/s41419-019-2102-3 |
| format | Article |
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473
and Thr
308
and subsequently downregulated matrix metalloproteinase 2 and 9, both of which are important proteins associated with VM formation and migration. Our results indicate that TNC plays an important role in VM formation in glioma, suggesting that TNC is a potential therapeutic target for anti-angiogenesis therapy for glioma.</description><identifier>ISSN: 2041-4889</identifier><identifier>EISSN: 2041-4889</identifier><identifier>DOI: 10.1038/s41419-019-2102-3</identifier><identifier>PMID: 31754182</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/105 ; 13/109 ; 13/51 ; 13/89 ; 13/95 ; 38/1 ; 38/109 ; 38/61 ; 38/90 ; 42 ; 631/136/16/1646 ; 631/67/2328 ; 631/67/327 ; 64/60 ; AKT protein ; Angiogenesis ; Antibodies ; Biochemistry ; Biomedical and Life Sciences ; Cell Biology ; Cell Culture ; Cell proliferation ; Gelatinase A ; Gelatinase B ; Glioma ; Glioma cells ; Immunology ; Invasiveness ; Life Sciences ; Matrix metalloproteinase ; Metalloproteinase ; Mimicry ; Phosphorylation ; Tenascin ; Tenascin C ; Therapeutic applications ; Tumor cells</subject><ispartof>Cell death & disease, 2019-11, Vol.10 (12), p.1-14, Article 879</ispartof><rights>The Author(s) 2019</rights><rights>2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3253-b639268ae2f59a044565f2051ed3fd9446b50fcf476316251e6460e16e5b54df3</citedby><cites>FETCH-LOGICAL-c3253-b639268ae2f59a044565f2051ed3fd9446b50fcf476316251e6460e16e5b54df3</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/PMC6872754/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872754/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids></links><search><creatorcontrib>Cai, Hai-ping</creatorcontrib><creatorcontrib>Wang, Jing</creatorcontrib><creatorcontrib>Xi, Shao-yan</creatorcontrib><creatorcontrib>Ni, Xiang-rong</creatorcontrib><creatorcontrib>Chen, Yin-sheng</creatorcontrib><creatorcontrib>Yu, Yan-jiao</creatorcontrib><creatorcontrib>Cen, Zi-wen</creatorcontrib><creatorcontrib>Yu, Zhi-hui</creatorcontrib><creatorcontrib>Chen, Fu-rong</creatorcontrib><creatorcontrib>Guo, Cheng-cheng</creatorcontrib><creatorcontrib>Zhang, Ji</creatorcontrib><creatorcontrib>Ke, Chao</creatorcontrib><creatorcontrib>Wang, Jian</creatorcontrib><creatorcontrib>Chen, Zhong-ping</creatorcontrib><title>Tenascin-c mediated vasculogenic mimicry formation via regulation of MMP2/MMP9 in glioma</title><title>Cell death & disease</title><addtitle>Cell Death Dis</addtitle><description>Vasculogenic mimicry (VM), the formation of vessel-like structures by highly invasive tumor cells, has been considered one of several mechanisms responsible for the failure of anti-angiogenesis therapy in glioma patients. Therefore, inhibiting VM formation might be an effective therapeutic method to antagonize the angiogenesis resistance. This study aimed to show that an extracellular protein called Tenascin-c (TNC) is involved in VM formation and that TNC knockdown inhibits VM in glioma. TNC was upregulated with an increase in glioma grade. TNC and VM formation are potential independent predictors of survival of glioma patients. TNC upregulation was correlated with VM formation, and exogenous TNC stimulated VM formation. Furthermore, TNC knockdown significantly suppressed VM formation and proliferation in glioma cells in vitro and in vivo, with a reduction in cellular invasiveness and migration. Mechanistically, TNC knockdown decreased Akt phosphorylation at Ser
473
and Thr
308
and subsequently downregulated matrix metalloproteinase 2 and 9, both of which are important proteins associated with VM formation and migration. Our results indicate that TNC plays an important role in VM formation in glioma, suggesting that TNC is a potential therapeutic target for anti-angiogenesis therapy for glioma.</description><subject>13/105</subject><subject>13/109</subject><subject>13/51</subject><subject>13/89</subject><subject>13/95</subject><subject>38/1</subject><subject>38/109</subject><subject>38/61</subject><subject>38/90</subject><subject>42</subject><subject>631/136/16/1646</subject><subject>631/67/2328</subject><subject>631/67/327</subject><subject>64/60</subject><subject>AKT protein</subject><subject>Angiogenesis</subject><subject>Antibodies</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Cell Biology</subject><subject>Cell Culture</subject><subject>Cell proliferation</subject><subject>Gelatinase A</subject><subject>Gelatinase B</subject><subject>Glioma</subject><subject>Glioma 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Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell death & disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cai, Hai-ping</au><au>Wang, Jing</au><au>Xi, Shao-yan</au><au>Ni, Xiang-rong</au><au>Chen, Yin-sheng</au><au>Yu, Yan-jiao</au><au>Cen, Zi-wen</au><au>Yu, Zhi-hui</au><au>Chen, Fu-rong</au><au>Guo, Cheng-cheng</au><au>Zhang, Ji</au><au>Ke, Chao</au><au>Wang, Jian</au><au>Chen, Zhong-ping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tenascin-c mediated vasculogenic mimicry formation via regulation of MMP2/MMP9 in glioma</atitle><jtitle>Cell death & disease</jtitle><stitle>Cell Death Dis</stitle><date>2019-11-21</date><risdate>2019</risdate><volume>10</volume><issue>12</issue><spage>1</spage><epage>14</epage><pages>1-14</pages><artnum>879</artnum><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>Vasculogenic mimicry (VM), the formation of vessel-like structures by highly invasive tumor cells, has been considered one of several mechanisms responsible for the failure of anti-angiogenesis therapy in glioma patients. Therefore, inhibiting VM formation might be an effective therapeutic method to antagonize the angiogenesis resistance. This study aimed to show that an extracellular protein called Tenascin-c (TNC) is involved in VM formation and that TNC knockdown inhibits VM in glioma. TNC was upregulated with an increase in glioma grade. TNC and VM formation are potential independent predictors of survival of glioma patients. TNC upregulation was correlated with VM formation, and exogenous TNC stimulated VM formation. Furthermore, TNC knockdown significantly suppressed VM formation and proliferation in glioma cells in vitro and in vivo, with a reduction in cellular invasiveness and migration. Mechanistically, TNC knockdown decreased Akt phosphorylation at Ser
473
and Thr
308
and subsequently downregulated matrix metalloproteinase 2 and 9, both of which are important proteins associated with VM formation and migration. Our results indicate that TNC plays an important role in VM formation in glioma, suggesting that TNC is a potential therapeutic target for anti-angiogenesis therapy for glioma.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31754182</pmid><doi>10.1038/s41419-019-2102-3</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 13/105 13/109 13/51 13/89 13/95 38/1 38/109 38/61 38/90 42 631/136/16/1646 631/67/2328 631/67/327 64/60 AKT protein Angiogenesis Antibodies Biochemistry Biomedical and Life Sciences Cell Biology Cell Culture Cell proliferation Gelatinase A Gelatinase B Glioma Glioma cells Immunology Invasiveness Life Sciences Matrix metalloproteinase Metalloproteinase Mimicry Phosphorylation Tenascin Tenascin C Therapeutic applications Tumor cells |
| title | Tenascin-c mediated vasculogenic mimicry formation via regulation of MMP2/MMP9 in glioma |
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