title: Melanoma cells produce multiple laminin isoforms and strongly migrate on α5 laminin(s) via several integrin receptors.
abstract: 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 LMα5 also promoted cell migration. Function-blocking antibodies in cell migration assays revealed α6β1 integrin as the major receptor for laminin-111, and both α3β1 and α6β1 integrins for laminin-332 and laminin-511. In contrast, isolated LMα5 IVa domain-promoted melanoma cell migration was largely mediated via αVβ3 integrin and inhibited by RGD peptides. Given the ubiquitous expression of α5 laminins in melanoma cells and in melanoma-target tissues/anatomical structures, as well as the strong migration-promoting activity of these laminin isoforms, the α5 laminins emerge as putative primary extracellular matrix mediators of melanoma invasion and metastasis via α3β1 and other integrin receptors.
authors.affiliation: Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Oikawa
authors.forename: Johan
authors.initials: J
authors.lastname: Hansson
authors.forename: Takako
authors.initials: T
authors.lastname: Sasaki
authors.forename: Patricia
authors.initials: P
authors.lastname: Rousselle
authors.forename: Anna
authors.initials: A
authors.lastname: Domogatskaya
authors.forename: Sergey
authors.initials: S
authors.lastname: Rodin
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
authors.forename: Manuel
authors.initials: M
authors.lastname: Patarroyo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D039201:Integrin alpha3beta1 / Q000378:metabolism*; D039121:Integrin alpha6beta1 / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D039201:Integrin alpha3beta1; D039121:Integrin alpha6beta1; D036341:Intercellular Signaling Peptides and Proteins; D007797:Laminin; D020033:Protein Isoforms; C097043:laminin alpha5