イノウエ　サトシ   Satoshi Inoue   井上　智    所属   川崎医科大学  医学部 臨床医学　脳神経外科学１    職種   講師
論文種別	研究論文（学術雑誌）
言語種別	英語
査読の有無	査読なし
表題	Bimodal anti-glioma mechanisms of cilengitide demonstrated by novel invasive glioma models
掲載誌名	正式名：NEUROPATHOLOGY ISSNコード：09196544/14401789
掲載区分	国外
巻・号・頁	33(2),pp.162-174
著者・共著者	Onishi Manabu, Ichikawa Tomotsugu, Kurozumi Kazuhiko, Fujii Kentaro, Yoshida Koichi, Inoue Satoshi, Michiue Hiroyuki, Chiocca E. Antonio, Kaur Balveen, Date Isao
発行年月	2013/04
概要	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.