Visfatin increases the invasive potential of ovarian granulosa tumor spheroids by reprogramming glucose metabolism

Abstract

Visfatin is an adipokine with nicotinamide phosphoribosyltransferase (NAMPT) activity, the concentration of which is higher in ascitic fluid than in serum, and is associated with ovarian cancer peritoneal dissemination. Furthermore, potentially important effects of visfatin on glucose metabolism have been previously reported. However, the mechanism underlying the effects of visfatin on ovarian cancer cell invasion, and whether this involves altered glucose metabolism, has not been elucidated. Here we tested the hypothesis that visfatin, which can reprogram cancer metabolism, promotes invasion by ovarian cancer spheroids. Visfatin increased glucose transporter (GLUT)1 expression and glucose uptake in adult granulosa cell tumor-derived spheroid cells (KGN), and also increased the activities of hexokinase 2 and lactate dehydrogenase. We showed a visfatin-induced increase in glycolysis in KGN cells. Moreover, visfatin increased the potential invasiveness of KGN spheroid cells by upregulating MMP2 (matrix metalloproteinase 2) and downregulating CLDN3 and CLDN4 (claudin 3 and 4) gene expression. Interestingly, an inhibitor of GLUT1 (STF-31) and lactate dehydrogenase (LDHA) abolished the stimulatory effect of visfatin on the potential invasiveness of KGN cells. More importantly, silencing expression of the NAMPT gene in KGN cells demonstrated its important effect on glycolysis and invasiveness in adult granulosa cell tumor cells. In summary, visfatin appears to increase adult granulosa cell tumor invasiveness through effects on glucose metabolism, and to be an important regulator of glucose metabolism in these cells

Mitochondria-targeted nanoparticles for encapsulating astaxanthin: exploring the reason for alleviating oxidative damage

“…Normal cells metabolize glucose to pyruvate through glycolysis, which enters the mitochondria where the tricarboxylic acid (TCA) cycle takes place [43]. During this process, oxygenation phosphorylation (OXPHOS) results in the production of ATP [44]. However, when the mitochondria function disordered, ATP cannot be produced through OXPHOS, and the cells need to maintain their energy supply by glycolytic activity.…”

Alteration of glucose metabolism and expression of glucose transporters in ovarian cancer

“…Moreover, the robust activation of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) signaling pathways has been described to promote epithelial ovarian carcinogenesis through the upregulation of GLUT proteins expression resulting in elevated glucose influx [ 17 ]. Besides, glucose metabolism alteration could display a significant role in the invasiveness and metastasis of epithelial and granulosa OC cells [ 18 ]. In this review, recent findings concerning GLUTs and disruption of glucose metabolism in OC are discussed as well as diagnostic and therapeutic approaches.…”