Abstract
Apelin and chemerin are adipocytokines that play important roles in many physiological and pathological processes throughout the body. Our previous study demonstrated that these two adipokines are expressed and secreted by epithelial and granulosa cancer cell lines. 17β-estradiol (E2) and insulin-like growth factor-1 (IGF-1) are important regulators of ovarian functions, and their roles are well known. This study investigated whether apelin and chemerin regulate proliferation and apoptosis of epithelial (OVCAR-3) and granulosa (COV434) ovarian cancer cell lines by interacting with E2 and IGF-1. Apelin and chemerin did not affect caspase-3 activation in either cell line. However, apelin abrogated the stimulatory effects of E2 on proliferation of OVCAR-3 cells and of IGF-1 on proliferation of COV434 cells independently of ERK1/2 and PI3K via crosstalk of apelin receptor with estrogen receptor alpha and IGF-1 receptor, respectively.
Highlights
Adipose tissue is one of the largest endocrine organs in the body and has endocrinologic, metabolic, and immunoregulatory roles
Apelin still increased cell proliferation following pretreatment with PHTPP or G15 (119 ± 7% and 117 ± 6%, respectively), and this effect was blocked in the presence of E2 (Fig. 4i, j). These results demonstrate that ERβ and G protein-coupled receptor 30 (GPR30) are not involved in the effects of apelin and E2 on cell proliferation and indicate that crosstalk occurs between apelin receptor (APLNR) and ERα
Our previous studies showed that apelin and chemerin are expressed in human ovarian cancer cell lines and that their expression ratio differs according to where the cells are derived from [7, 8]
Summary
Adipose tissue is one of the largest endocrine organs in the body and has endocrinologic, metabolic, and immunoregulatory roles. Several reports indicate that ovarian cells express adipose tissue hormones, called adipokines, and their receptors [1,2,3,4,5,6]. Our previous studies demonstrated that ovarian cancer cells express adipokine receptors and synthesize and secrete adipokines such as apelin [7] and chemerin [8]. These findings suggest that apelin and chemerin have paracrine and autocrine actions in ovarian cancer cells. Our laboratory recently reported that the basal apelin concentration in epithelial and granulosa cancer cells is approximately 0.4 and 0.6 ng/ ml, respectively [7]. Recent studies demonstrated that apelin expression is increased in various cancers, including those of the colon [18], lung [13, 19], and oral cavity [20]
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