Reduction of invasive potential in K-ras-transformed thyroid cells by restoring of TGF-b pathway

Transforming Growth Factor-beta1 (TGF-b1) is a multifunctional cytokine that regulates a number of cellular processes such as cell growth, differentiation, plasticity, cell motility, adhesiveness, embryogenesis, development and apoptosis through binding to TGF-b receptors. We have previously demonstrated that K-ras-transformed rat thyroid cells, K10, are resistant to the growth inhibitory action of TGF-b1, because they show a decreased expression of type II receptor (TbRII). Clones obtained transfecting TbRII, partially revert their malignant phenotype, showing a reduction in the anchorage-dependent and -independent cell growth and a statistically significant decrease in tumourigenicity with respect to the highly malignant parental cells, both in spontaneous and artificial metastases, when transplanted in athymic nude mice. The purpose of the present work is to elucidate the molecular events involved in the modulation of the tumourigenic potential of K-ras-transformed rat thyroid cells overexpressing TbRII. Our data demonstrate that the TbRII overexpressed in K-ras-transformed thyroid cell clones is a functional receptor and is essential to restore in these cells behaviour similar to that of control cells. The TbRII overexpression is responsible for a strong reduction of adhesive and migratory behaviour of highly malignant K-ras-transformed thyroid cells. These results suggest that the restore of a functional TGF-b receptor in these cells may be useful for the limitation of tumour spread and dissemination.