Fiche publication
Date publication
février 2016
Journal
International journal of cancer
Auteurs
Membres identifiés du Cancéropôle Est :
Dr PEIXOTO Paul
Tous les auteurs :
Fahmy K, Gonzalez A, Arafa M, Peixoto P, Bellahcène A, Turtoi A, Delvenne P, Thiry M, Castronovo V, Peulen O
Lien Pubmed
Résumé
Pancreatic ductal adenocarcinoma is one of the most deadly forms of cancers with no satisfactory treatment to date. Recent studies have identified myoferlin, a ferlin family member, in human pancreas adenocarcinoma where its expression was associated to a bad prognosis. However, the function of myoferlin in pancreas adenocarcinoma has not been reported. In other cell types, myoferlin is involved in several key plasma membrane processes such as fusion, repair, endocytosis and tyrosine kinase receptor activity. In this study, we showed that myoferlin silencing in BxPC-3 human pancreatic cancer cells resulted in the inhibition of cell proliferation in vitro and in a significant reduction of the tumor volume in chick chorioallantoic membrane assay. In addition to be smaller, the tumors formed by the myoferlin-silenced cells showed a marked absence of functional blood vessels. We further demonstrated that this effect was due, at least in part, to an inhibition of VEGFA secretion by BxPC-3 myoferlin-silenced cells. Using immunofluorescence and electron microscopy, we linked the decreased VEGFA secretion to an impairment of VEGFA exocytosis. The clinical relevance of our results was further strengthened by a significant correlation between myoferlin expression in a series of human pancreatic malignant lesions and their angiogenic status evaluated by the determination of the blood vessel density.
Mots clés
Adenocarcinoma, blood supply, Antigens, CD31, analysis, Calcium-Binding Proteins, analysis, Carcinoma, Pancreatic Ductal, blood supply, Cell Line, Tumor, Cell Proliferation, Humans, Membrane Proteins, analysis, Muscle Proteins, analysis, Neovascularization, Pathologic, etiology, Pancreatic Neoplasms, blood supply, Vascular Endothelial Growth Factor A, analysis
Référence
Int. J. Cancer. 2016 Feb;138(3):652-63
