Expression Levels of Adiponectin Receptors are Decreased in Human Endometrial Adenocarcinoma Tissues

Abstract

Adiponectin is a cytokine secreted by adipocytes, whose plasma levels are decreased in obesity. Adiponectin has insulin-sensitizing, antiatherogenic, and antidiabetogenic effects. It has been shown that adiponectin may also exert antineoplastic activity through suppression of tumor proliferation and neoangiogenesis and through induction of apoptosis. Recently, low adiponectin serum concentration has been found in obesity-related malignancies, including endometrial cancer. In addition, the expression of adiponectin receptors (AdipoR1 and AdipoR2) has been documented in several human cancer tissues, but the expression has previously not been assessed in human endometrial cancer tissues. In this study, we analyzed the immunohistochemical expression of AdipoR1 and AdipoR2 in a series of surgically resected human endometrioid adenocarcinoma tissues from a total of 141 cases. Decreased AdipoR1 or AdipoR2 expression was significantly associated with histological higher grade (P=0.0026 and 0.0004, respectively). Decreased expression of AdipoR1 was associated with myometrial invasion and lymph node metastasis of endometrioid adenocarcinoma (P=0.0039 and P=0.0069, respectively). AdipoR1 and AdipoR2 immunoexpression was significantly associated with the expression of the progesterone receptor, although it was not significantly correlated with the expression of the estrogen receptor, Ki-67 or p53. Our present study raises the possibility that decreased expression of adiponectin receptors is implicated in the development, invasion, and metastasis of human endometrioid adenocarcinoma. Our findings, moreover, indicate that adiponectin receptors could be considered as therapeutic targets for endometrioid adenocarcinoma. In adiponectin receptor-positive endometrioid adenocarcinoma, we think adiponectin-based anticancer therapy is useful; however, in histological high-grade endometrioid adenocarcinoma, in which the expression levels of adiponectin receptors are relatively low, adiponectin therapy supported by adiponectin receptor induction is needed.

Evaluating vaspin and adiponectin in postmenopausal women with endometrial cancer

“…Decreased adiponectin receptor 1 (AdipoR1)/AdipoR2 expression has also been shown to be closely associated with neoplastic growth of the endometrium. Investigators reported lower levels of AdipoR1 in endometrial adenocarcinoma patients with myometrial invasion or lymph node metastasis (Yamauchi et al 2012). It has been postulated that adiponectin may prevent tumorigenesis by activating AMPK and inhibiting phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling via AdipoR1/2 (Schmandt et al 2011).…”

Adipose tissue, obesity and adipokines: role in cancer promotion

“…Henece, adiponectin receptor expression decrese is a proposed contributor to cancer progression and currently is a proposed target of treatment for endometrioid adenocarcinomas [69]. In one study, KLE and RL95-2 human endometrial cancer cell lines had a decrease in proliferation when incubated with adiponectin [70].…”

“…Decreased adiponectin receptor expression is associated with a histological higher grade of endometrial cancer [69]. Henece, adiponectin receptor expression decrese is a proposed contributor to cancer progression and currently is a proposed target of treatment for endometrioid adenocarcinomas [69].…”

Features of Endometrial Cancer in Patients With ‘Metabolically Healthy’ Versus ‘Standard’ Obesity: the Decreasing Frequency of Metabolically Healthy Obesity

“…Here we briefly mention the following supportive observations. First of all, leptin and adiponectin receptor density in EC tumor tissue correlates directly for leptin and inversely for adiponectin receptors, with regional lymph nodes involvement [48,49]. On the other hand, total serum testosterone levels tend to be higher in patients with EC [50] as it occurs in postmenopausal women with developing insulin resistance [51].…”