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

Abstract

We have previously shown that 2 human melanoma cell lines, the metastatic HT-144 and the non-metastatic SK-Mel-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-beta1, thus identifying TGF-beta as an autocrine regulator of the spindle shape morphology of HT-144 melanoma cells. The fibroblastoid phenotype correlated with up-regulated beta1 and beta3 integrin and down-regulated 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-beta1-dependent up-regulation of integrin-linked kinase and the nuclear translocation of beta-catenin, 2 intracellular proteins involved in integrin and cadherin signaling.