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Basic Information

Gene ID

3911

Name

LAMA5

Synonymous

laminin, alpha 5;LAMA5;laminin, alpha 5

Definition

laminin alpha-5 chain|laminin subunit alpha-5|laminin-10 subunit alpha|laminin-11 subunit alpha|laminin-15 subunit alpha

Position

20q13.2-q13.3

Gene type

protein-coding

Title

Abstract

melanoma

Melanoma cells express and interact with laminins (LMs) and other basement membrane components during invasion and metastasis. In the present study we have investigated the production and migration-promoting activity of laminin isoforms in melanoma. Immunohistochemistry of melanoma specimens and immunoprecipitation/western blotting of melanoma cell lines indicated expression of laminin-111/121, laminin-211, laminin-411/421, and laminin-511/521. Laminin-332 was not detected. In functional assays, laminin-111, laminin-332, and laminin-511, but not laminin-211 and laminin-411, strongly promoted haptotactic cell migration either constitutively or following stimulation with insulin-like growth factors. Both placenta and recombinant laminin-511 preparations were highly active, and the isolated recombinant IVa domain of LMalpha5 also promoted cell migration. Function-blocking antibodies in cell migration assays revealed alpha6beta1 integrin as the major receptor for laminin-111, and both alpha3beta1 and alpha6beta1 integrins for laminin-332 and laminin-511. In contrast, isolated LMalpha5 IVa domain-promoted melanoma cell migration was largely mediated via alphaVbeta3 integrin and inhibited by RGD peptides. Given the ubiquitous expression of alpha5 laminins in melanoma cells and in melanoma-target tissues/anatomical structures, as well as the strong migration-promoting activity of these laminin isoforms, the alpha5 laminins emerge as putative primary extracellular matrix mediators of melanoma invasion and metastasis via alpha3beta1 and other integrin receptors.