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ID 50689
フルテキストURL
著者
Onishi, Manabu Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg
Ichikawa, Tomotsugu Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg Kaken ID researchmap
Kurozumi, Kazuhiko Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg Kaken ID researchmap
Fujii, Kentaro Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg
Yoshida, Koichi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg
Inoue, Satoshi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg
Michiue, Hiroyuki Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg Kaken ID
Chiocca, E. Antonio Brigham & Womens Faulkner Hosp, Dept Neurosurg
Kaur, Balveen Ohio State Univ, Dept Neurol Surg, Dardinger Lab Neurooncol & Neurosci
Date, Isao Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg ORCID Kaken ID publons researchmap
抄録
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.
キーワード
angiogenesis
animal model
glioma
integrin
invasion
発行日
2013-04
出版物タイトル
Neuropathology
33巻
2号
開始ページ
162
終了ページ
174
ISSN
0919-6544
資料タイプ
学術雑誌論文
オフィシャル URL
http://dx.doi.org/10.1111/j.1440-1789.2012.01344.x
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/50658
言語
English
論文のバージョン
author
査読
有り
DOI
Web of Science KeyUT