Melanoma cells produce multiple laminin isoforms and strongly migrate on alpha 5 laminin(s) via several integrin receptors

作者：Oikawa Yuko; Hansson Johan; Sasaki Takako; Rousselle Patricia; Domogatskaya Anna; Rodin Sergey; Tryggvason Karl; Patarroyo Manuel^*

来源：Experimental Cell Research, 2011, 317(8): 1119-1133.

DOI：10.1016/j.yexcr.2010.12.019

• Melanoma
• Laminin
• Integrin
• Migration

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 LM alpha 5 also promoted cell migration. Function-blocking antibodies in cell migration assays revealed alpha 6 beta 1 integrin as the major receptor for laminin-111, and both alpha 3 beta 1 and alpha 6 beta 1 integrins for laminin-332 and laminin-511. In contrast, isolated LM alpha 5 IVa domain-promoted melanoma cell migration was largely mediated via alpha V beta 3 integrin and inhibited by RGD peptides. Given the ubiquitous expression of alpha 5 laminins in melanoma cells and in melanoma-target tissues/anatomical structures, as well as the strong migration-promoting activity of these laminin isoforms, the alpha 5 laminins emerge as putative primary extracellular matrix mediators of melanoma invasion and metastasis via alpha 3 beta 1 and other integrin receptors.

• 出版日期2011-5-1