INTEGRIN ALPHA-3-BETA-1-MEDIATED INTERACTION WITH LAMININ-5 STIMULATES ADHESION, MIGRATION AND INVASION OF MALIGNANT GLIOMA-CELLS

Gliomas, characterized by their progressively invasive phenotype, expr ess integrin alpha 3 beta 1 as a major receptor for the extracellular matrix both in vivo and in vitro. Since the integrin alpha 3 beta 1 ha s been shown to be a specific receptor for laminin-5 (alpha 3 beta 3 g amma 2), we examined the effects of purified human laminin-5 on adhesi on, migration and invasion of human glioma cells. Among different type s of laminin variants and other matrix proteins including fibronectin and vitronectin, laminin-5 was most potent in promoting adhesion and m igration of different kinds of glioma cells. Laminin-5-mediated adhesi on and migration were specifically inhibited by monoclonal antibodies against integrin alpha 3 and beta 1 chains, confirming the role of int egrin alpha 3 beta 1 as the major laminin-5 receptor. Invasion of the reconstituted basement membrane (i.e., Matrigel) by glioma cells was a lso selectively stimulated by laminin-5. Out results show that laminin -5 is the major extracellular stimulant for glioma cell adhesion, migr ation and invasion. The immunohistochemical distribution of laminin ga mma 2 chain, a laminin subunit unique to laminin-5, showed that it was expressed in the tumor parenchyma of human glioma tissues. Expression of laminin alpha 3, beta 3 and gamma 2 chains in glioma tissues and i n glioma cell lines was also demonstrated at the messenger RNA level b y reverse transcription polymerase chain reaction. Our results, taken together, show that laminin-5 may be involved in the invasive phenotyp e of malignant gliomas both in vitro and in vivo. (C) 1998 Wiley-Liss, Inc.