No abstract

Abstract. Development of metastasis is a major cause of death for squamous cell carcinoma of the head and neck (sccHn) patients. epithelial to mesenchymal transition (eMt) is now regarded as a correlate of tumor metastasis. given that transforming growth factor-β1 (tgF-β1) is an important inducer of eMt, we examined the effects of tgF-β1 on the human sccHn cell line tu686. We found that tgF-β1 mediated cell morphological changes. phasecontrast microscopy revealed a loss of the adherent phenotype with cellular elongation, decrease in cell-to-cell contact, and the induction of a fibroblast-like state. Western blotting and reverse transcriptase-polymerase chain reaction (rt-pcr) analysis demonstrated that tgF-β1 could induce down-regulation of the epithelial marker e-cadherin and up-regulation of the mesenchymal marker vimentin in tu686 cells in a concentration-and time-dependent manner. Woundhealing and transwell invasion assay indicated that tgF-β1 promoted tu686 cell migration and invasion dramatically. In addition, these changes were mediated via canonical tgF-β/ smad signaling with concomitant up-regulation of phosphorylated smad2. smad2 rnAi abrogated both expression and functional effects of tgF-β1 on tu686 cells. In conclusion, the present study demonstrates that tgF-β1 could induce EMT in the SCCHN cell line via the TGF-β/Smad signaling pathway. More importantly, a cell model for eMt was established, which is valuable for future studies on the metastasis of sccHn.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent malignancy with a 5-year survival rate of 54%. Therefore, disease management improvement is required. The present study aimed to assess the role of caveolin-1 (Cav-1) in the metastasis of head and neck tumor cells. Short hairpin RNA was used to silence Cav-1 expression in Tu686 cells. Proliferation, migration, invasion, morphology and the levels of effector proteins were assessed in cells. Upon Cav-1 silencing, E-cadherin levels were decreased, while vimentin levels were significantly increased. Cell migration, quantified by wound healing and Transwell assays, was significantly increased. Meanwhile, Cav-1 and transforming growth factor β1 (TGF-β1) receptor were identified to be co-localized. In addition, Cav-1knockdown resulted in increased phosphorylation of SMAD family member 2 (P<0.05), a downstream effector of TGF-β signaling. In addition, there was a mutual regulation, with increasing TGF-β1 levels leading to a dose-dependent decrease of Cav-1 expression levels (P<0.05). These findings indicate that Cav-1 inhibits cell metastasis in HNSCC, suggesting the involvement of the TGF-β signaling pathway.