ECM DEPENDENT AND INTEGRIN-MEDIATED TUMOR-CELL MIGRATION OF HUMAN GLIOMA AND MELANOMA CELL-LINES UNDER SERUM-FREE CONDITIONS

Collagen IV, laminin and fibronectin are consitituents of the cerebral extracellular matrix (ECM), which is critical in glioma cell invasion . The aim of the present study was to evaluate the integrin dependent cell-matrix interactions of two tumors with different invasive propert ies under matrixfree conditions. Two human glioma (GaMG, U373) and mel anoma (MV3, BLM) cell lines were grown in serum free medium. Immunoflu orescence microscopy of collagen IV, laminin, and fibronectin was perf ormed. The adhesion of monolayer cells and their migration out of mult icellular spheroids was quantified for these ECM components. Integrin chains known to act as laminin receptors were blocked by specific anti bodies in additional migration assays. All cell lines expressed all th e ECM components under serum free conditions. Tumor cell adhesion and migration in both glioma and melanoma cell lines was increased by all the ECM components, laminin being the strongest promotor of migration. However, migration was dose dependent in gliomas, whereas melanomas r evealed a dose optimum of 10 mu g/ml laminin. Antibodies against alpha 3 integrins significantly reduced migration on laminin in all cell li nes, anti-beta 1 in all cell lines except U373. Anti-alpha 2 in BLM sh owed a strong effect, anti-alpha 6 was a stronger inhibitor in glioma than in melanoma cells. Integrins are functionally involved in tumor c ell locomotion on laminin. The blocking of laminin related integrin ch ains markedly reduced cell motility in a varying manner between the ce ll lines. Moreover, different cell lines utilize different integrins a s the laminin receptor.