Premium
α v ‐Integrin antagonist EMD 121974 induces apoptosis in brain tumor cells growing on vitronectin and tenascin
Author(s) -
Taga Takashi,
Suzuki Atsushi,
GonzalezGomez Ignacio,
Gilles Floyd H.,
Stins Monique,
Shimada Hiroyuki,
Barsky Lora,
Weinberg Kenneth I.,
Laug Walter E.
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10265
Subject(s) - vitronectin , tenascin , tenascin c , integrin , fibronectin , angiogenesis , cancer research , apoptosis , biology , microbiology and biotechnology , endothelial stem cell , chemistry , extracellular matrix , cell , in vitro , biochemistry
Orthotopic brain tumor growth is inhibited in athymic mice by the daily systemic administration of the α v ‐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 α v ‐integrin interaction with the matrix proteins vitronectin and tenascin. Here we show that EMD 121974 also induces apoptosis in the α v ‐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 α v ‐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 α v ‐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. © 2002 Wiley‐Liss, Inc.