RESUMEN
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.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , MicroARNs , Neoplasias de la Boca , Humanos , Carcinoma de Células Escamosas/patología , Proteínas Portadoras/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/genética , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias de la Boca/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Animales , PerrosRESUMEN
SLUG, encoded by the Snai2 gene, is known to play a role in epithelial-mesenchymal transition (EMT), which contributes to cell invasion and metastasis in some types of human carcinomas. However, the mechanisms and roles of EMT in canine squamous cell carcinoma (SCC) have not yet been elucidated. We have previously established canine oral SCC cell lines, including tonsillar SCC, and in this study, we evaluated the effects of SLUG on the phenotypes regarding EMT of canine SCC cells. First, immunohistochemical analysis revealed that SLUG is upregulated in canine oral SCC tissues compared to that in non-tumoural oral mucosa. Furthermore, gain-of-function and loss-of-function of SLUG revealed that SLUG partly contributed to migration and invasion of cells, as well as the upregulation of EMT markers such as vimentin and SNAIL. Thus, the current study suggests that SLUG promotes cell migration and invasion through EMT induction in canine oral SCC, as well as human cancers.
Asunto(s)
Carcinoma de Células Escamosas , Enfermedades de los Perros , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Animales , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/veterinaria , Línea Celular Tumoral , Enfermedades de los Perros/patología , Perros , Transición Epitelial-Mesenquimal/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/veterinaria , Neoplasias de la Boca/patología , Neoplasias de la Boca/veterinaria , Invasividad Neoplásica/genética , Factores de Transcripción de la Familia Snail/genética , Factores de Transcripción de la Familia Snail/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/veterinariaRESUMEN
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.