Melanoma cells produce multiple laminin isoforms and strongly migrate on α5 laminin(s) via several integrin receptors
| Autor: | Karl Tryggvason, Sergey Rodin, Manuel Patarroyo, Takako Sasaki, Johan Hansson, Patricia Rousselle, Anna Domogatskaya, Yuko Oikawa |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Gene isoform
Integrin Extracellular matrix Cell Movement Laminin Cell Line Tumor medicine Animals Humans Protein Isoforms Neoplasm Invasiveness Receptor Melanoma Integrin alpha6beta1 biology Integrin alpha3beta1 Cell migration Cell Biology medicine.disease Molecular biology Blot biology.protein Cytokines Intercellular Signaling Peptides and Proteins |
| Zdroj: | Experimental Cell Research. 317:1119-1133 |
| ISSN: | 0014-4827 |
| DOI: | 10.1016/j.yexcr.2010.12.019 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect