RESUMO
OBJECTIVES: Canine oral squamous cell carcinoma (SCC) often develops in the gingiva and tonsils. The biological behavior of canine oral SCC is similar to that of human head and neck SCC (HNSCC). Inhibiting invasion and metastasis is major importance for the treatment of canine and human HNSCC. In this study, the significance of microRNA (miR)-145 and Fascin1 (FSCN1) in the invasion of canine oral SCC was explored. MATERIALS AND METHODS: Canine oral SCC tissues and cell lines were used for miR-145 and FSCN1 expression analysis via real-time PCR and immunohistochemistry. Canine oral SCC cell lines were used for in vitro assays. RESULTS: miR-145 was downregulated while FSCN1 mRNA was upregulated in canine oral SCC. Immunohistochemistry revealed that FSCN1 was upregulated in SCC when compared to normal mucosa. Transfection of canine SCC cells with miR-145 or FSCN1 siRNA suppressed cell growth and attenuated cell migration as well as invasion by inhibiting the epithelial-to-mesenchymal transition. Furthermore, the promoter region of miR-145 was highly methylated in SCC cell lines and tissues. CONCLUSION: The expression profile and functions of miR-145 in canine oral SCC are similar to those in human HNSCC. Thus, canine oral SCC may represent a valuable preclinical model for human HNSCC.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , MicroRNAs , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/patologia , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Bucais/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Animais , CãesRESUMO
Canine tonsillar squamous cell carcinoma (TSCC) shows a higher metastasis rate than non-tonsillar oral SCC (NTSCC). The mechanisms of metastasis for TSCC have been less studied, because both TSCC and NTSCC cell lines are few. In this study, 6 cloned TSCC (TSCCLN#1-#6), which were from a metastatic lymph node, and 2 cloned NTSCC (oSCC-1 and -4) cell lines, which were from the primary lesion, were established, and their characteristics were evaluated in vitro and in vivo. Results showed that increased expression level of Vimentin in TSCC cell lines and increased expression levels of mesenchymal markers including Vimentin, Snail, and Slug in NTSCC cell lines corelated with the malignant phenotypes such as the cell growth and colony formation abilities in vitro. However, expression levels of mesenchymal markers and in vitro characteristics were unrelated to tumorigenic ability in nude mice. Additionally, the expression levels of E-cadherin and Vimentin were also evaluated by immunohistochemistry using the formalin-fixed paraffin embedded canine oral SCC tissues, and the results show that the expression level of Vimentin in TSCC was higher than in NTSCC. In conclusion, the cell lines established in this study might contribute to elucidating the mechanisms involved in TSCC metastasis.
