Overexpression of caveolin‐1 in a human melanoma cell line results in dispersion of ganglioside GD3 from lipid rafts and alteration of leading edges, leading to attenuation of malignant properties

Caveolin‐1 is a component of lipid rafts, and is considered to be a tumor suppressor molecule. However, the mechanisms by which caveolin‐1 functions in cancer cells are not well understood. We generated caveolin‐1 transfectant cells (Cav‐1+ cells) using a human melanoma cell line (SK‐MEL‐28) and investigated the effects of caveolin‐1 overexpression on the GD3‐mediated malignant properties of melanomas. Cav‐1+ cells had decreased cell growth and motility, and reduced phosphorylation levels of p130Cas and paxillin relative to controls. In floatation analysis, although GD3 was mainly localized in glycolipid‐enriched microdomain (GEM)/rafts in control cells, it was dispersed from GEM/rafts in Cav‐1+ cells. Correspondingly, GD3 in Cav‐1+ cells stained uniformly throughout the membrane, whereas control cells showed partial staining of the membrane, probably at the leading edge. p130Cas and paxillin were stained in the leading edges and colocalized with GD3 in the control cells. In contrast, these molecules were diffusely stained and no definite leading edges were detected in Cav‐1+ cells. These results suggest that caveolin‐1 regulates GD3‐mediated malignant signals by altering GD3 distribution and leading edge formation. These results reveal one of the mechanisms by which caveolin‐1 curtails the malignant properties of tumor cells. (Cancer Sci 2007; 98: 512–520)