Reduction of invasive potential in K-ras-transformed thyroid cells by restoring of TGF-beta pathway.
Transforming Growth Factor-beta1 (TGF -beta1) 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-beta receptors. We have previously demonstrated that K-ras-transformed rat thyroid cells, K10, are resistant to the growth inhibitory action of TGF-beta1, because they show a decreased expression of type II receptor (TbetaRII). Clones obtained transfecting TbetaRII, 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 TbetaRII. Our data demonstrate that the TbetaRII 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 TbetaRII 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-beta receptor in these cells may be useful for the limitation of tumour spread and dissemination.
Nicolussi
Arianna
A
Department of Experimental Medicine and Pathology, University La Sapienza, V.le Regina Elena, 324, 00161 Rome, Italy.
D'Inzeo
Sonia
S
Gismondi
Angela
A
Coppa
Anna
A
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002461:Cell Line, Transformed / Q000187:drug effects / Q000473:pathology; D002465:Cell Movement / Q000502:physiology*; D002472:Cell Transformation, Viral; D002999:Clone Cells; D004353:Drug Evaluation, Preclinical; D005353:Fibronectins; D011905:Genes, ras; D006801:Humans; D007797:Laminin; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D017346:Protein Serine-Threonine Kinases; D021381:Protein Transport; D051381:Rats; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D051901:Smad4 Protein / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D005353:Fibronectins; D007797:Laminin; D018125:Receptors, Transforming Growth Factor beta; D011993:Recombinant Fusion Proteins; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D051901:Smad4 Protein; C490811:Smad4 protein, rat; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II