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 α3β1 as a major receptor for the extracellular matrix both in vivo and in vitro. Since the integrin α3β1 has been shown to be a specific receptor for laminin-5 (α3β3γ2), 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 α3 and β1 chains, confirming the role of integrin α3β1 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 γ2 chain, a laminin subunit unique to laminin-5, showed that it was expressed in the tumor parenchyma of human glioma tissues. Expression of laminin α3, β3 and γ2 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. Int. J. Cancer76:63–72, 1998.© 1998 Wiley-Liss, Inc.