| IntroductionOral squamous cell carcinoma(OSCC)is one of the most common epithelial malignant neoplasma,which is one of higher morbidity carcinomas all over the world.OSCC can seriously jeopardize the lives and quality of life.Therefore,the occurrence and development of OSCC mechanism has always been one of hot spots of oral cancer researchers.Local recurrences and regional neck lymph nodes metastasis are the prominent clinical features of OSCC,which are also the hallmarks of epithelial malignancy.It is the direct and major cause of patient's recurrence and death.One of the main mechanisms for tumor invasion and metastasis is epithelial-mesenchymal transition(EMT).Gelsolin is one of the actin binding proteins(ABPs),which can assemble and disassemble actin filaments,and then regulate the cytoskeleton and cell motility.Gelsolin may influence OSCC invasion and metastasis via EMT.To clarify the role of gelsolin in OSCC invasion and metastasis,the clinicopathologic significance and expression of gelsolin in oral tissues were investigated,and further studies focus on the effect on OSCC motility and EMT.Research results will contribute to understanding the biological mechanism of OSCC invasion and metastasis.Materials and methods1.The expression of gelsolin in 10 cases of normal oral mucosa,36 cases of oral leukoplakia and 119 cases of OSCC was investigated with immunohistochemistry;Gelsolin expression level by quantitative reverse-transcription-PCR(qRT-PCR)was compared between tumor focus and peritumoral normal tissue in 27 cases;The relationship between gelsolin expression and clinical pathological parameters of OSCC was also analyzed.2.The gelsolin of HSC-3 was overexpressed by plasmid transfection,and the gelsolin expression was inhibited by RNA interference.The effect of gelsolin on HSC-3 motility was evaluated by wound healing assay and Transwell migration assay.3.Exogenous transforming growth factor-?1(TGF-?1)was used to induce the HSC-3 EMT,and then the gelsolin,epithelial markers and mesenchymal markers were detected at different observed times.Meanwhile,after the gelsolin expression was downregulated by RNA interference,the epithelial markers and mesenchymal markers were detected.Results1.In conventional paraffin sections,the gelsolin in human OSCC lesions showed a significant lower expression than that in normal oral mucosa or oral leukoplakia.However,there was no difference between normal oral mucosa and oral leukoplakia.2.The gelsolin expression in patients older than 70 years was the highest among age groups.There was a lower gelsolin expression in the patients with invasion of the adjacent anatomic sites,advanced stage or lymph nodes metastasis.However,there was no significant different on the gelsolin expression in different gender and histological grade.3.In fresh OSCC tissues,the gelsolin mRNA expression in tumor focus had relatively lower than that in peritumoral normal tissue.Moreover,the gelsolin mRNA expression in human head and neck cancer cell lines was lower than that in human immortalized oral epithelial cells.4.The down-regulation of gelsolin in HSC-3 can promote cell migration.Meanwhile,the gelsolin overexpression can inhibit cell migration.5.TGF-?1 triggered EMT in HSC-3,accompanied with the down-regulation of gensolin in this process.Furthermore,after the gelsolin expression in HSC-3 was inhibited by RNA interference,the down-regulation of epithelial markers and up-regulation of mesenchymal markers were observed.Conclusions1.The gelsolin expression in human OSCC is lower than that in normal oral mucosa and precancerous lesions,which may indicate that gelsolin is a tumor suppressor gene in OSCC tumorigenesis.2.The development of clinical stage,the enlargement of tumor size and neck lymph nodes metastasis mean reduced gelsolin expression,which suggest that down-regulation of gelsolin may promote OSCC progression.3.The down-regulation of gelsolin can induce EMT and enhance cells motility,which may be one of essential intrinsic mechanism of OSCC progression. |
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