Abstract
The expression of adiponectin receptors AdipoR1 and AdipoR2 has been reported in the human ovary and ovarian cancer tissues. Moreover, adiponectin has been reported to act as an anti-tumor factor by inhibiting cancer cell proliferation. Thus, we investigate whether adiponectin and its receptors influence ovarian cancer development. In the present study, we found that adiponectin was not expressed in the granulosa cell line (COV434), and epithelial ovarian cancer cell lines (OVCAR-3, SKOV-3, and Caov-3). Additionally, we found that AdipoR1 and AdipoR2 expression is lower in epithelial ovarian cancer cells than in granulosa tumor cells. Endogenous 17β-estradiol as well as exogenous estrogens, such as bisphenol A and its chlorinated and brominated analogs do not affect adiponectin receptor expression. We found that adiponectin inhibited the growth of OVCAR-3 and SKOV-3 cells, and that this effect was independent of apoptosis. Moreover, adiponectin reverses the stimulatory effects of 17β-estradiol and insulin-like growth factor 1 on cell proliferation by downregulating the expression of their receptors, whereas progesterone increased the sensitivity of cancer cells to adiponectin by upregulating AdipoR1 and AdipoR2 expression. These results suggest interactions between adiponectin and various ovarian steroid hormone and growth factor pathways in ovarian cancer cells.
Highlights
IntroductionDue to its non-specific symptoms, most cases of ovarian cancer are detected when the disease has advanced to a late stage that associates with poor survival
Ovarian cancer remains the leading cause of death among women, with an estimated 150,000 annual deaths worldwideHighlights Adiponectin receptor expression is lower in epithelial ovarian cancer cells than in granulosa tumor cells. Adiponectin represses the proliferation of epithelial ovarian cancer cells. Estrogens, such as E2 and bisphenol A (BPA) and its analogs, do not affect adiponectin receptor expression. Progesterone potentiates the effects of adiponectin by upregulating the expression of its receptors. Adiponectin reverses the proliferative effects of E2 and insulin-like growth factor 1 (IGF-1) by downregulating the expression of its receptors.[1]
We aimed to investigate whether adiponectin and its receptors, AdipoR1 and AdipoR2, are expressed in human epithelial ovarian cancer cell lines
Summary
Due to its non-specific symptoms, most cases of ovarian cancer are detected when the disease has advanced to a late stage that associates with poor survival. Approaches that would increase its early detection are urgently needed to reduce mortality. Ovarian cancer can be classified into three types based on the cell of its origin, namely, epithelial, stromal, and germ, with each type conferring different histopathological features and clinical outcomes [2]. Epithelial ovarian cancer is the most common ovarian malignancy; it originates in epithelial cells found on the surface of the ovary and accounts for ~ 80–90% of ovarian malignancies. On the other hand, account for ~ 7% of ovarian malignancies, and the most frequently diagnosed stromal tumor type is the granulosa cell tumor (GCT)
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