2013年4月
Bimodal anti-glioma mechanisms of cilengitide demonstrated by novel invasive glioma models
NEUROPATHOLOGY
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- 巻
- 33
- 号
- 2
- 開始ページ
- 162
- 終了ページ
- 174
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1111/j.1440-1789.2012.01344.x
- 出版者・発行元
- WILEY-BLACKWELL
Integrins are expressed in tumor cells and tumor endothelial cells, and likely play important roles in glioma angiogenesis and invasion. We investigated the anti-glioma mechanisms of cilengitide (EMD121974), an v3 integrin inhibitor, utilizing the novel invasive glioma models, J3T-1 and J3T-2. Immunohistochemical staining of cells in culture and brain tumors in rats revealed positive v3 integrin expression in J3T-2 cells and tumor endothelial cells, but not in J3T-1 cells. Established J3T-1 and J3T-2 orthotopic gliomas in athymic rats were treated with cilengitide or solvent. J3T-1 gliomas showed perivascular tumor cluster formation and angiogenesis, while J3T-2 gliomas showed diffuse single-cell infiltration without obvious angiogenesis. Cilengitide treatment resulted in a significantly decreased diameter of the J3T-1 tumor vessel clusters and its core vessels when compared with controls, while an anti-invasive effect was shown in the J3T-2 glioma with a significant reduction of diffuse cell infiltration around the tumor center. The survival of cilengitide-treated mice harboring J3T-1 tumors was significantly longer than that of control animals (median survival: 57.5 days and 31.8 days, respectively, P<0.005), while cilengitide had no effect on the survival of mice with J3T-2 tumors (median survival: 48.9 days and 48.5, P=0.69). Our results indicate that cilengitide exerts a phenotypic anti-tumor effect by inhibiting angiogenesis and glioma cell invasion. These two mechanisms are clearly shown by the experimental treatment of two different animal invasive glioma models.
- リンク情報
-
- DOI
- https://doi.org/10.1111/j.1440-1789.2012.01344.x
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/22989076
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861321
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000317018700006&DestApp=WOS_CPL
- ID情報
-
- DOI : 10.1111/j.1440-1789.2012.01344.x
- ISSN : 0919-6544
- PubMed ID : 22989076
- PubMed Central 記事ID : PMC4861321
- Web of Science ID : WOS:000317018700006