Integrin α3β1-mediated interaction with laminin-5 stimulates adhesion, migration and invasion of malignant glioma cells

Gliomas, characterized by their progressively invasive phenotype, express 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 has been shown to be a specific receptor for laminin-5 (alpha 3 beta 3 gamma 2), we examined the effects of purified human laminin-5 on adhesion, migration and invasion of human glioma cells. Among different types of laminin variants and other matrix proteins including fibronectin and vitronectin, laminin-5 was most potent in promoting adhesion and migration of different kinds of glioma cells. Laminin-5-mediated adhesion and migration were specifically inhibited by monoclonal antibodies against integrin alpha 3 and beta 1 chains, confirming the role of integrin alpha 3 beta 1 as the major laminin-5 receptor. Invasion of the reconstituted basement membrane (i.e., Matrigel) by glioma cells was also selectively stimulated by laminin-5. Out results show that laminin-5 is the major extracellular stimulant for glioma cell adhesion, migration and invasion. The immunohistochemical distribution of laminin gamma 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 in glioma cell lines was also demonstrated at the messenger RNA level by reverse transcription polymerase chain reaction. Our results, taken together, show that laminin-5 may be involved in the invasive phenotype of malignant gliomas both in vitro and in vivo. (C) 1998 Wiley-Liss, Inc.