Antiproliferative Effects of Adiponectin on Human Trophoblastic Cell Lines JEG-3 and BeWo1

Abstract

During embryo implantation, a complex dialog exists between the mother and the fetus. However, little is known about the molecules that participate in this process. Among various factors secreted at the maternal-fetal interface, the adipose tissue-derived leptin is now considered a placental growth factor. Adiponectin is another adipocyte-derived signaling molecule known to exert antiproliferative effects in various cell types. In this work, we studied adiponectin sensitivity and effects on JEG-3 and BeWo choriocarcinoma cell lines. First, we showed that JEG-3 and BeWo cells express the specific adiponectin receptors ADIPOR1 and ADIPOR2 and respond to human recombinant adiponectin by AMP-activated protein kinase (PRKA, also known as AMPK) activation. Second, we demonstrated that adiponectin induces a reduction in cell number and in [(3)H]-thymidine incorporation, demonstrating that adiponectin has antiproliferative effects on trophoblastic cells. Furthermore, these effects of adiponectin seem to be, at least in part, mediated by the mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase (PI3K) signaling pathways. We describe herein the direct effects of adiponectin in the control of trophoblastic cell proliferation.

Effects of adiponectin on human trophoblast invasion

“…Trophoblast infiltration of Some cytokines, such as IL6, IL10, IL11, leukemia inhibitory factor, epidermal growth factor, angiotensin II, and leptin, have recently been described to modulate synthesis and release of one or more of these MMPs and TIMPs (Castellucci et al 2000, Gonzalez et al 2001, Qiu et al 2004, Araki-Taguchi et al 2008, Fitzgerald et al 2008, Pang et al 2008. Adiponectin is another cytokine that seemed to play an important role in embryo implantation (Caminos et al 2005, Takemura et al 2006b, Benaitreau et al 2009, McDonald & Wolfe 2009). The presence of adiponectin at the feto-maternal interface originates firstly to human endometrium.…”

“…Furthermore, it was demonstrated that, in human endometrium, adiponectin receptor levels are the highest during the luteal period, which corresponds to the embryo implantation period (Takemura et al 2006a). More recently, we have shown in our laboratory that adiponectin exerts anti-proliferative effects on trophoblastic cell lines JEG-3 and BeWo and also on human trophoblasts (Benaitreau et al 2009). McDonald & Wolfe (2009 have shown that adiponectin reduces the endocrine function of human term placenta.…”

Expression of Adiponectin Receptor 1 Is Indicative of Favorable Prognosis in Non-small Cell Lung Carcinoma

“…Therefore, there has been great interest in determining whether adiponectin has a protective role in carcinogenesis (Kelesidis et al 2006;Byeon et al 2010). Adiponectin has anti-angiogenic (Molica et al 2009), anti-proliferative (Dos Santos et al 2008;Benaitreau et al 2009), and proapoptotic effects, and also arrests cancer cell growth (Kang et al 2005;Cong et al 2007), having both direct effects on carcinogenesis and indirect effects through alteration of hor-mones and cytokine levels (Kelesidis et al 2006).…”

Adiponectine et résistine

“…En revanche, celle d'AdipoR2 diminue et n'est pas affectée par la restriction alimentaire [40]. L'adiponectine diminue la prolifération in vitro des lignées trophoblastiques JEG-3 et BeWo [41], stimule la différen-ciation du trophoblaste villeux en syncytiotrophoblaste et favorise la sécrétion d'hormones placentaires, de l'hCG (hormone chorionique gonadotrope), et de leptine. Le profil d'expression de la résistine placentaire n'est pas encore connu.…”