Actin organization and cell migration of melanoma cells relate to differential expression of integrins and actin-associated proteins.

We have recently described marked differences in cell migration rates and organization of actin in human melanoma cell lines isolated from various stages of tumor progression. Metastatic lines derived from lymph node metastases organized actin into stress fiber arrays and had high mean migration rates in vitro when compared to lines from other stages. Melanoma cells also reveal marked differences in localization of alpha-actinin and beta 1 integrins at stress fiber termination sites (focal contacts). Disruption of this organization is induced by antibodies against beta 1 integrins, alpha-actinin, recently postulated as having a role in linkage of actin to beta 1 integrins, is differentially expressed in melanoma cells by Northern blot analysis and a relatively high alpha-actinin to actin ratio is associated with stress fiber formation and increased cell migration. Furthermore, actin-binding protein, which cross-links actin filaments, is also significantly increased in lines exhibiting high migration rates. Control of migration and actin organization may be mediated by extracellular matrices and/or modulation of actin-associated proteins including alpha-actinin and actin binding protein. These findings provide evidence that an interaction of transmembrane adhesion molecules and elements of the cytoskeleton in melanoma cells may be responsible for differences in migration rates and capacity for metastasis.