期刊
INTERNATIONAL JOURNAL OF CANCER
卷 98, 期 5, 页码 690-697出版社
WILEY-LISS
DOI: 10.1002/ijc.10265
关键词
brain tumor; xenograft; anti-angiogenesis; alpha nu-integrins; apoptosis
类别
资金
- NCI NIH HHS [CA 82989] Funding Source: Medline
- NHLBI NIH HHS [HL 54850] Funding Source: Medline
Orthotopic brain tumor growth is inhibited in athymic mice by the daily systemic administration of the alphav-integrin antagonist EMD 121974. This compound, a cyclic RGD-penta-peptide, is a potent inhibitor of angiogenesis, which induces apoptosis of growing endothelial cells through inhibition of their av-integrin interaction with the matrix proteins vitronectin and tenascin. Here we show that EMD 121974 also induces apoptosis in the alphav-integrin-expressing tumor cell lines U87 MG and DAOY by detaching them from vitronectin and tenascin, matrix proteins known to be essential for brain tumor growth and invasion. These matrix proteins are shown to be produced by the brain tumor cells in vitro and in vivo. Furthermore, only tumor cells expressing alphav-integrins responded to the treatment with EMD 121974, after xenotransplantation into the forebrain of nude mice, supporting the importance of tumor cell-matrix interactions in tumor cell survival in the brain. Thus, the alphav-antagonist EMD 121974 suppresses brain tumor growth through induction of apoptosis in both brain capillary and brain tumor cells by preventing their interaction with the matrix proteins vitronectin and tenascin. The dual action of this peptide explains its potent growth suppression of orthotopically transplanted brain tumors. (C) 2002 Wiley-Liss, Inc.
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