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 beta 1 (TGF-beta 1). Here, we studied the effect of suppressing TGF-beta 1 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-beta 1 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-beta 1-silenced mucoepidermoid carcinoma cells, as compared to controls.CONCLUSION: These results unveil a critical role for TGF-beta 1 in the progression of mucoepidermoid carcinomas and suggest that patients with this malignancy may benefit from therapeutic inhibition of the effectors of the TGF-beta 1 pathway. J Oral Pathol Med (2011) 40: 762-768