Transforming growth factor (TGF)-β1 is a multifunctional 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-β1 and TGF-β 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-β1 enhanced the migration and invasion of OSCC cells, TRI significantly suppressed the migration and invasion of these cells. Exogenous TGF-β1 up-regulated the activity of type IV collagenase (gelatinase A and gelatinase B), whereas TRI down-regulated the activity of these matrix metalloproteinases. Western blot analysis revealed that TGF-β1 enhanced the expression of α5, αv, β1, β6 and αvβ3 integrin subunits, and these enhanced integrins were down-regulated by treatment with TRI. These results suggest that the inhibition of TGF-β1 suppresses motility and invasiveness of OSCC cells via modulation of integrins and matrix-metalloproteinases. Therefore, targeting the TGF-β1 signaling pathway could be beneficial in the treatment of patients with OSCC.

Related Articles