RESUMEN
Epithelial-mesenchymal transition (EMT) is a crucial step in tumour progression. However, the molecular mechanisms underlying EMT in canine tumours remain to be elucidated. In this study, the similarity or difference in the molecular mechanism of EMT in canine cells was evaluated and compared with that reported in human and mouse cells. We used eight cell lines derived from canine mammary cancers. Stimulation with hepatocyte growth factor (HGF) increased cell motility and changed EMT-related markers towards mesenchyme in CHMm cell line. These changes were accompanied by an increase in Twist expression and did not occur in CHMm transfected with Twist siRNA, indicating that Twist plays a key role in this phenomenon in CHMm. However, the down-regulation of E-cadherin was not observed by HGF stimulation. Further studies are required to elucidate the difference between human and canine Twist.
Asunto(s)
Enfermedades de los Perros/genética , Transición Epitelial-Mesenquimal , Regulación de la Expresión Génica , Neoplasias Mamarias Animales/genética , Proteína 1 Relacionada con Twist/genética , Regulación hacia Arriba , Secuencia de Aminoácidos , Animales , Biomarcadores/metabolismo , Línea Celular Tumoral , Movimiento Celular , Enfermedades de los Perros/fisiopatología , Perros , Femenino , Factor de Crecimiento de Hepatocito/genética , Factor de Crecimiento de Hepatocito/metabolismo , Humanos , Neoplasias Mamarias Animales/fisiopatología , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/genética , Transfección , Proteína 1 Relacionada con Twist/química , Proteína 1 Relacionada con Twist/metabolismoRESUMEN
It is known that epithelial mesenchymal transition (EMT) contributes to the acquisition of malignant property in human cancers. However, the role of EMT in canine tumors remains to be elucidated. To evaluate the correlation between expression levels of protein markers involved in EMT and clinicopathological characteristics in canine mammary gland tumors, immunohistochemistry using antibodies against ZO-1, E-cadherin, vimentin, N-cadherin and fibronectin was performed on 119 clinical tissue samples. Consequently, loss of ZO-1 and E-cadherin, and gain of vimentin and N-cadherin were more frequently observed in malignant tumors than in benign tumors. However, there was no correlation among expression of these molecules. Univariate and multivariate analysis identified that loss of E-cadherin independently had a low one-year survival rate (adjusted odds ratio: 2.3, P=0.02). These results suggested that EMT might relate to acquisition of malignancy, and additionally, E-cadherin was strongly correlated with malignant behavior in canine mammary gland tumors.
Asunto(s)
Adenocarcinoma/veterinaria , Adenoma/veterinaria , Biomarcadores de Tumor/metabolismo , Enfermedades de los Perros/metabolismo , Regulación Neoplásica de la Expresión Génica/fisiología , Neoplasias Mamarias Animales/metabolismo , Adenocarcinoma/clasificación , Adenocarcinoma/metabolismo , Adenoma/clasificación , Adenoma/metabolismo , Animales , Biomarcadores de Tumor/genética , Enfermedades de los Perros/genética , Enfermedades de los Perros/patología , Perros , Transición Epitelial-Mesenquimal/fisiología , FemeninoRESUMEN
Epithelial-mesenchymal transition (EMT) is a fundamental phenomenon in organisms that occurs during gastrulation, wound healing, and cancer metastasis. Various cytokines induce EMT processes through complex mechanisms. Inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), induce EMT in human cell lines. However, whether inflammatory cytokines can affect EMT processes in canine cell lines remains unclear. In this study, we investigated the role of transforming growth factor beta (TGF-ß), TNF-α, and IL-6 in Madin-Darby canine kidney (MDCK) cells. We found that the localization of E-cadherin, a cell adhesion molecule, was shifted and that its expression was decreased. We also observed morphological changes in MDCK cells under persistent stimulation of inflammatory cytokines. Morphological changes in cells may occur during late stages of EMT processes; inflammatory cytokines may be important in these changes.