2022 Volume 31 Issue 3 Pages 171-180
Although TGF-β is known to be related to tumor proliferation, invasion and epithelial-mesenchymal transition (EMT), its effects on oral carcinomas remain unclear. This study aimed to elucidate the effects of TGF-β on oral squamous cell carcinoma (OSCC). In the present in vitro study, three human OSCC cell lines; SAS (tongue cancer), Ca9-22 (mandibular gingival cancer) and HSC-3 (cervical lymph nodes metastasis of tongue cancer), were treated with TGF-β1 or TGF-β signaling inhibitors, and assayed for proliferation and invasion. Expressions of EMT-related markers; E-Cadherin, N-Cadherin, Snail and Slug, as well as matrix metalloproteinases (MMPs) were evaluated by immunofluorescence staining and RT-qPCR. TGF-β1 treatment induced morphological change of SAS to spindle shape, significant proliferation of SAS and Ca9-22 (p<0.05), and significant increase in invasion capacity of all three cell lines (p<0.05). Inhibition of TGF-β signaling significantly suppressed proliferation of all three cell lines (p<0.05). By treatment with TGF-β1, reduced expression of E-Cadherin and enhanced expressions of N-Cadherin, Snail and Slug were observed in SAS (poorly differentiated OSCC), whereas E-Cadherin expression was enhanced in Ca9-22 (well differentiated OSCC) and variable depending on TGF-β1 concentration in HSC-3 (lymph node metastatic OSCC). Expressions of MMPs were enhanced in all three OSCC cell lines. TGF-β1 increases proliferation and invasion capacity of OSCC cell lines, while TGF-β signaling inhibition suppresses proliferation. TGF-β1 treatment may induce EMT by enhancing transcription activity, suppressing epithelial markers and augmenting mesenchymal markers in poorly differentiated OSCC, but induce both mesenchymal-epithelial transition (MET) and EMT depending on TGF-β1 concentration in lymph node metastatic OSCC. TGF-β1-induced enhancement of MMP expression may be associated with increased invasion capacity.
