Autocrine TGF-beta-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 H T-144 and the non-metastatic SK-Mel-2 cells, exhibit marked in vitro hetero geneity with respect to integrin expression, migration and invasion potenti al. Here, we provide evidence that HT-144 melanoma cells, but not SK-Mel-2 cells, undergo a reversible transition to a fibroblastoid morphology follow ing treatment with either their own serum-free acidified conditioned medium or biologically active exogenous TGF-beta 1, thus identifying TGF-beta as an autocrine regulator of the spindle shape morphology of HT-144 melanoma c ells. The fibroblastoid phenotype correlated with up-regulated beta 1 and b eta 3 integrin and downregulated E-cadherin expression, as shown by flow cy tometry, Western blot and RT-PCR, as well as up-regulated expression of the matrix metalloproteinase MMP-9, as demonstrated by zymography. Our data fu rther illustrate the TOP-beta 1-dependent up-regulation of integrin-linked kinase and the nuclear translocation of beta-catenin, 2 intracellular prote ins involved in integrin and cadherin signaling. (C) 1999 Wiley-Liss, Inc.