Direct role of adiponectin and adiponectin receptors in endometrial cancer: in vitro and ex vivo studies in humans
Menée sur des lignées cellulaires et des échantillons tumoraux de cancer de l'endomètre, cette étude analyse le rôle de l'adiponectine et des ses récepteurs dans la prolifération cellulaire et le processus invasif
Low adiponectin levels are an independent risk factor for, and mediate the effect of obesity on endometrial cancer in epidemiology studies. The direct or indirect mechanisms underlying these findings remain to be elucidated. We first examined the expression of adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2) in normal human endometrium and in endometrial cancer tissues ex vivo. We then utilized KLE and RL95-2 human endometrial cancer cell lines in vitro to study relative expression of AdipoRs, to investigate the effect of adiponectin on activating intracellular signaling pathways, and to assess its potential to alter malignant properties. We report for the first time that the relative expression level of AdipoR1 is higher than AdipoR2 in human endometrial cancer tissue but the expression of AdipoRs is not statistically different from non-neoplastic tissues. We also demonstrate for the first time in endometrial cancer cell lines in vitro that adiponectin suppresses endometrial cancer proliferation acting through AdipoRs. Adiponectin also increases the expression of the adaptor molecule LKB1 which is required for adiponectin-mediated activation of AMPK/S6 axis and modulation of cell proliferation, colony formation, adhesion and invasion of KLE and RL95-2 cell lines. These novel mechanistic studies provide for the first time in vitro and ex vivo evidence for a causal role of adiponectin in endometrial cancer.
http://mct.aacrjournals.org/content/early/2011/10/06/1535-7163.MCT-11-0545.abstract