Gynaecological cancers and leptin: A focus on the endometrium and ovary

Keywords:

Leptin, obesity, ovarian epithelium, pelvic mass, uterine cancer


Published online: Nov 21 2018

A. Ray 1, J. Fornsaglio 2, S. Dogan 3, S. Hedau 4, D. Naik SL 5, A. De 6

1 Lake Erie College of Osteopathic Medicine, Seton Hill University, Greensburg, PA 15601, United States;
2 School of Natural & Health Sciences, Seton Hill University, Greensburg, PA 15601, United States;
3 Department of Medical Biology, School of Medicine, Yeditepe University, Istanbul, 34755, Turkey;
4 National Institute of Cancer Prevention & Research (ICMR), Noida 201301, U.P., India,
5 National Institute of Traditional Medicine (ICMR), Belagavi 590010, Karnataka, India;
6 Ovarian Cancer Laboratory, Veterans Affairs Medical Center, Kansas City, MO 64128, United States.

Abstract

Obesity has an influence on the risk and prognosis of different types of cancers of the female reproductive tract. In the uterus, a common site for neoplasms is the endometrium, the inner lining tissue. Generally, obesity has been documented to be involved in endometrioid carcinoma of the endometrium. Obesity may influence the cancer risk by various mechanisms such as chronic inflammation, dysregulation of sex hormones and abnormal secretion of hormone-like cytokines or adipokines from adipose tissue. One of the important pro-inflammatory adipokines is leptin, which acts via its transmembrane receptors (Ob-R). In normal conditions, leptin functions in the hypothalamic anorexigenic pathway to maintain the energy homeostasis. Conversely, in obesity, leptin participates in the pro-inflammatory processes. Several clinical studies have suggested that leptin and Ob-R play a role in the pathological processes of endometrial cancer. In different endometrial cancer cell lines, laboratory findings also have demonstrated leptin’s link to various neoplastic phenomena such as cellular proliferation, angiogenesis, and oestrogenic activity. Furthermore, endometrial cancer risk could be increased in ovarian pathology like polycystic ovary syndrome, which is commonly associated with obesity. It is noteworthy that leptin participates in both physiological and pathological conditions of the ovary. Leptin has shown pro-tumorigenic effects in both in-vitro and in-vivo studies. Generally, reduced serum leptin levels have been observed in ovarian cancer patients. However, overexpression of leptin and Ob-R in ovarian cancer tissue has indicated aggressive disease. Understanding the role of leptin-related intracellular signalling pathways in tumour development could be helpful in early cancer detection.