Inhibition of TGF-β1 suppresses motility and invasiveness of oral squamous cell carcinoma cell lines via modulation of integrins and down-regulation of matrix-metalloproteinases

Transforming growth factor (TGF)-beta 1 is a multi functional polypeptide that regulates a variety of cellular processes. Several studies have indicated that it is associated with epithelial-mesenchymal transition, angiogenesis, migration and metastases in many types of malignant tumors. We have used a wound-healing assay and a Matrigel invasion assay to evaluate the effects of TGF-beta 1 and TGF-beta receptor I kinase inhibitor (TRI) on the cell motility and invasiveness of the human oral squamous cell carcinoma (OSCC) cell lines SAS-L1 and HSC-3. While TGF-beta 1 enhanced the migration and invasion of OSCC cells, TRI significantly suppressed the migration and invasion of these cells. Exogenous TGF-beta 1 up-regulated the activity of type W collagenase (gelatinase A and gelatinase B), whereas TRI down-regulated the activity of these matrix metalloproteinases. Western blot analysis revealed that TGF-beta 1 enhanced the expression of alpha 5, alpha v, beta 1, beta 6 and alpha v beta 3 integrin Subunits, and these enhanced integrins were down-regulated by treatment with TRI. These results suggest that the inhibition of TGF-beta 1 suppresses motility and invasiveness of OSCC cells via modulation of integrins and matrix-metalloproteinases. Therefore, targeting the TGF-beta 1 signaling pathway Could be beneficial in the treatment of patients with OSCC.