Role of laminin receptor in tumor cell migration.
Polyclonal antisera were made against biochemically purified laminin receptor protein as well as against synthetic peptides deduced from a complementary DNA clone corresponding to the COOH-terminal end of the laminin receptor (U.M. Wewer et al., Proc. Natl. Acad. Sci. USA, 83: 7137-7141, 1986). These antisera were used to study the potential role of laminin receptor in laminin-mediated attachment and haptotactic migration of human A2058 melanoma cells. The anti-laminin receptor antisera reacted with the surface of suspended, nonpermeabilized melanoma and carcinoma cells. The anti-laminin receptor antisera blocked the surface interaction of A2058 cells with endogenous laminin, resulting in the inhibition of laminin-mediated cell attachment. The A2058 melanoma cells migrated toward a gradient of solid phase laminin or fibronectin (haptotaxis). Anti-laminin antiserum abolished haptotaxis on laminin but not on fibronectin. Synthetic peptide GRGDS corresponding to the fibronectin cell-binding domain inhibited haptotaxis on fibronectin but not on laminin. Both types of anti-laminin receptor antisera inhibited haptotaxis on laminin but not on fibronectin. Using immunohistochemistry, invading human carcinoma cells in vivo exhibited a marked cytoplasmic immunoreactivity for the receptor antigen. Together these findings indicate a specific role for the laminin receptor in laminin-mediated migration and that the ligand binding of the laminin receptor is encompassed in the COOH-terminal end of the protein.
D002448:Cell Adhesion; D002465:Cell Movement; D004797:Enzyme-Linked Immunosorbent Assay; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007797:Laminin / Q000378:metabolism; D008545:Melanoma / Q000473:pathology; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000473:pathology*; D011971:Receptors, Immunologic / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D017474:Receptors, Laminin
D005353:Fibronectins; D007106:Immune Sera; D007797:Laminin; D011971:Receptors, Immunologic; D017474:Receptors, Laminin