Targeting TGF-ß1 suppresses survival of and invasion by anaplastic thyroid carcinoma cells.

BACKGROUND AND AIMS: Overexpression of transforming growth factor (TGF)-ß1 has been implicated in promoting cell survival, migration and invasion in many cancers, including anaplastic thyroid cancer (ATC). In the present study, we studied the effect of suppressing TGF-ß1 by RNA silencing on the survival, invasion and metastasis of ATC cells. METHODS: Small interfering RNA (siRNA) constructs targeting TGF-ß1 were validated and used to develop clonal derivatives of the ATC cell line, 8505C. The cells were used in several in vitro assays, including migration, invasion, survival rate, colony formation and apoptosis. A wound healing assay was used to determine the migration of cells in culture and a Boyden chamber transwell assay was used for invasion. Further, clones were used in an in vivo mouse model to study the kinetics of tumor growth and metastatic growth in lungs. RESULTS: Targeting TGF-ß1 expression in 8505C cells caused a 70% decrease in migration and a 78% decrease in invasion, as well as a 68% decrease in proliferation and a 19% increase in apoptosis in vitro. The growth of primary tumors in vivo was also inhibited when compared with parental 8505C cells; however, the number of mice bearing lung metastases was not significantly decreased. CONCLUSIONS: Targeting TGF-ß1 may be effective in inhibiting primary tumor formation, but not metastasis, by ATC cells. TGF-ß1 inhibition in combination with other tumor-targeted therapies may be more effective in inhibiting ATC.