Integrin alpha3beta1-mediated interaction with laminin-5 stimulates adhesion, migration and invasion of malignant glioma cells.
Gliomas, characterized by their progressively invasive phenotype, express integrin alpha3beta1 as a major receptor for the extracellular matrix both in vivo and in vitro. Since the integrin alpha3beta1 has been shown to be a specific receptor for laminin-5 (alpha3beta3gamma2), 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 alpha3 and beta1 chains, confirming the role of integrin alpha3beta1 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 gamma2 chain, a laminin subunit unique to laminin-5, showed that it was expressed in the tumor parenchyma of human glioma tissues. Expression of laminin alpha3, beta3 and gamma2 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.
Fukushima
Y
Y
Research Institute, Osaka Medical Center for Maternal and Child Health, Izumi, Japan.
Ohnishi
T
T
Arita
N
N
Hayakawa
T
T
Sekiguchi
K
K
D015703:Antigens, CD / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D017077:Culture Media, Conditioned; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D039422:Integrin alpha3; D016023:Integrins / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011994:Recombinant Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000097794:Kalinin
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D039422:Integrin alpha3; D016023:Integrins; D007797:Laminin; D011994:Recombinant Proteins; D000097794:Kalinin; C058783:laminin beta2