Autocrine TGF-β-regulated expression of adhesion receptors and integrin-linked kinase in HT-144 melanoma cells correlates with their metastatic phenotype

We have previously shown that 2 human melanoma cell lines, the metastatic HT-144 and the non-metastatic SKMel-2 cells, exhibit marked in vitro heterogeneity with respect to integrin expression, migration and invasion potential. Here, we provide evidence that HT-144 melanoma cells, but not SK-Mel-2 cells, undergo a reversible transition to a fibroblastoid morphology following treatment with either their own serum-free acidified conditioned medium or biologically active exogenous TGF-β1, thus identifying TGF-β as an autocrine regulator of the spindle shape morphology of HT-144 melanoma cells. The fibroblastoid phenotype correlated with up-regulated β1 and β3 integrin and downregulated E-cadherin expression, as shown by flow cytometry, Western blot and RT-PCR, as well as up-regulated expression of the matrix metalloproteinase MMP-9, as demonstrated by zymography. Our data further illustrate the TGF-β1-dependent up-regulation of integrin-linked kinase and the nuclear translocation of β-catenin, 2 intracellular proteins involved in integrin and cadherin signaling.