Publication: Cambios proteómicos y del metabolismo energético en un modelo "in vitro" de interacción epitelio-mesenquimal de cáncer de páncreas
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2017-09-07
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Universidad Complutense de Madrid
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Abstract
El adenocarcinoma ductal de páncreas es un tumor con una gran capacidad de invasión y metástasis. La transición epitelio mesenquimal (EMT) es un conjunto de procesos por los que la célula tumoral incrementa dicha capacidad, que son reversibles y están asociados con mecanismos epigenéticos y de disregulación metabólica, que a su vez tienen efectos transitorios en la transcripción génica. Los fibroblastos asociados al cáncer (CAF) son el componente celular más abundante del estroma tumoral y colaboran en la promoción del tumor primario y en la generación del nicho metastásico. El cáncer de páncreas se asocia a una gran reacción desmoplásica, caracterizada por proliferación fibroblástica y secreción de matriz extracelular, que puede constituir hasta el 70% del volumen tumoral. El TGF- está implicado en la activación de las células estromales del cáncer de páncreas y en la de los procesos de transición epitelio-mesenquimal de las células tumorales. Paradójicamente, la inactivación de SMAD4, frecuente en cáncer de páncreas, que impide la señalización por TGF-, se asocia a un incremento de la capacidad de metástasis...
Ductal adenocarcinoma is a tumour with a great potential to invade tissues and metastasize. Epithelial-mesenchimal transition (EMT) is a set of reversible processes that confers tumor cell a greater ability to migrate and develop distant metastases. EMT is associated with epigenetic mechanisms and metabolic disregulation, which have transient effects in gene transcription. Cancer associated fibroblasts (CAF) are the most frequent cell type in tumor stroma, that cooperate with the tumor in cancer promotion and in conditioning the metastatic niche. Pancreatic cancer is associated wih a great desmoplastic reaction. This is characterized by fibroblasts proliferation and extracellular matrix generation, and can constitute 70% of the tumour volume. TGF- is involved in the activation of both stromal cells and EMT processes in tumor cells. However, SMAD4, a member of TGF- signaling pathway, is frequently inactivated in pancreas adenocarcinoma. Nevertheless, this fact is associated to an increase of its metastatic behaviour...
Ductal adenocarcinoma is a tumour with a great potential to invade tissues and metastasize. Epithelial-mesenchimal transition (EMT) is a set of reversible processes that confers tumor cell a greater ability to migrate and develop distant metastases. EMT is associated with epigenetic mechanisms and metabolic disregulation, which have transient effects in gene transcription. Cancer associated fibroblasts (CAF) are the most frequent cell type in tumor stroma, that cooperate with the tumor in cancer promotion and in conditioning the metastatic niche. Pancreatic cancer is associated wih a great desmoplastic reaction. This is characterized by fibroblasts proliferation and extracellular matrix generation, and can constitute 70% of the tumour volume. TGF- is involved in the activation of both stromal cells and EMT processes in tumor cells. However, SMAD4, a member of TGF- signaling pathway, is frequently inactivated in pancreas adenocarcinoma. Nevertheless, this fact is associated to an increase of its metastatic behaviour...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Medicina, leída el 18-01-2016