The Role of the Adipokine Resistin in the Pathogenesis and Progression of Epithelial Ovarian Cancer

Abstract

Obesity is a civilization disease associated with an increased risk of developing cardiovascular diseases, diabetes, and some malignancies. The results concerning the relationship between obesity and epithelial ovarian cancer (EOC) are inconclusive. The higher incidence of neoplasms in obese subjects has led to the development of the adipokine hypothesis. Omental adipocyte cells interact with cancer cells, promoting their migration and metastasis via the secretion of adipokines, growth factors, and hormones. One of the adipokines is resistin. It was shown in vitro that resistin stimulates the growth and differentiation of ovarian cancer cells. Moreover, it increases the level of angiogenesis factors, e.g., matrix metalloproteinase 2 (MMP-2) and vascular epithelial growth factor (VEGF). Additionally, resistin induces epithelial–mesenchymal transition (EMT) and stemness in EOC cell lines. A positive correlation has been shown between a higher level of resistin expression and the stage of histological differentiation of EOC or the occurrence of lymph node metastases. In addition, the overexpression of resistin has been found to act as an independent factor determining disease-free survival as well as overall survival in EOC patients. Growing evidence supports the finding that resistin plays an important role in some mechanisms leading to the progression of EOC, though this issue still requires further research.

Adipocytokines and Insulin Resistance: Their Role as Benign Breast Disease and Breast Cancer Risk Factors in a High-Prevalence Overweight-Obesity Group of Women over 40 Years Old

“…Based on these results, we could hypothesize that the decreased resistin level in BBD may be a biochemical marker of metabolic alterations related to the development of BC and other neoplasms such as epithelial ovarian cancer, endometrial cancer, and esophageal squamous cell carcinoma [29][30][31].…”

The Role of Selected Adipocytokines in Ovarian Cancer and Endometrial Cancer

“…Current reports indicate that abnormal expression of resistin and its receptors are found in the course of many malignancies, particularly breast cancer, esophageal squamous cell carcinoma, gastric cancer, endometrial adenocarcinoma and ovarian cancer [ 183 , 184 , 185 ]. The potential role of resistin in carcinogenesis is shown in Figure 5 .…”

“…Resistin stimulates the synthesis of TNF-α, IL-6 and IL-12 (Interleukin 12) in adipocytes and immune cells involved in ovarian cancer progression. It has also been found that cancer cells are capable of directly synthesizing these factors, resulting in in vitro expression of TNF-α and IL-6 1000-fold higher in cancer cells compared to physiological ovarian epithelial cells [ 184 ]. Studies by Pang et al [ 53 ] indicate that resistin is capable of promoting and progressing ovarian cancer cells, which was associated with the growth of resistin-stimulated SKOV3 and CAOV3 lineage cells.…”

“…In addition, it was shown that resistin positively correlates with tumor cell migration in ovarian cancer, contributing to ovarian cancer progression. Resistin in ovarian cancer interacts via the PI3K-Akt-Sp1 signaling pathway to stimulate the synthesis of MMP-2 and VEGF and lead to the formation of new blood vessels [ 184 ]. Qiu et al [ 186 ], in their culture studies on A2780 and SKOV-3 lines, confirm resistin’s involvement in VGF and MMP-2 factor-mediated angiogenesis.…”

Omentum provides a special cell microenvironment for ovarian cancer

“…The exiting results have revealed that the higher level of resistin, the poorer prognosis of ovarian cancer. It can enhance the angiogenesis process, epithelial‐mesenchymal transition and stemness of ovarian cancer cells 24 . Recombinant human resistin enhanced the expression of VEGF in a time‐ and dose‐dependent manner in human ovarian cancer cell lines.…”