Alterations in Tgf-β Signaling Mediate the Biologic Behaviour of Osteosarcoma Cell Lines

Osteosarcoma is a mesenchymal tumour of bone common among children and young adults. Prognosis is poor if metastases are present at diagnosis. The transforming growth factor beta (TGF-β) signaling pathway plays a complex dual role in cancer. We hypothesized that alterations in the TGF-β signaling pathway are important in the tumorigenesis of osteosarcoma cell lines. Smad phosphorylation and nuclear localization, Smad4 expression, and TAZ expression were determined in the HOS osteosarcoma cell line and tumorigenic derivatives. Basal TGF-β activity and TAZ expression correlated with a tumorigenic phenotype in the KHOS cell lines as measured by Anchorage Independent Growth (AIG). In comparison, exogenous TGF-β suppressed AIG and acted as a tumour suppressor, while Smad4-deficient KHOS cells were resistant to the inhibitory TGF-β effect. In conclusion, basal TGF-β signaling and TAZ correlate with increased tumorigenic potential in osteosarcoma cell lines, whereas exogenous TGF-β acted as a tumour suppressor in a Smad4-dependent manner.MAS