TGF-β1 regulates the invasive and metastatic potential of mucoepidermoid carcinoma cells.

BACKGROUND Patients with mucoepidermoid carcinoma exhibit poor long-term prognosis because of the lack of therapeutic strategies that effectively block tumor progression. We have previously characterized the Ms cells as a highly metastatic mucoepidermoid carcinoma cell line that expresses high levels of transforming growth factor β1 (TGF-β1). Here, we studied the effect of suppressing TGF-β1 by RNA silencing on the invasive and metastatic potential of mucoepidermoid carcinoma. METHODS Cell motility, substratum adhesion, and transmembrane invasion were estimated by migration, matrigel adhesion, and matrigel invasion assay. Matrix metalloproteinase (MMP)-2 and MMP-9 activity were determined using gelatin gel zymography. Balb/c nu/nu nude mice lung metastatic model was used to test the metastatic ability of the Ms cells. Lung metastatic tumors were experimentally induced by mice tail vein inoculation of cancer cells. RESULTS TGF-β1 silencing inhibits cell motility, substratum adhesion, and transmembrane invasion. In vivo, a significant decrease in lung metastasis was observed when mice received tail vein injections of TGF-β1-silenced mucoepidermoid carcinoma cells, as compared to controls. CONCLUSION These results unveil a critical role for TGF-β1 in the progression of mucoepidermoid carcinomas and suggest that patients with this malignancy may benefit from therapeutic inhibition of the effectors of the TGF-β1 pathway.