Table 3.

Adipokines and cytokines implicated in EOC development and poor outcomes.

Cytokine	Change under condition of metabolic abnormalities	Mechanism contributing to EOC development and progression
IL-6 Source: Adipocytes [73], macrophages [73], tumor cells	Increased in obesity and DM [74] Reduced in primates [75] and postmenopausal women under calorie restriction Increased by higher levels of ROS [76]	Promotes angiogenesis Induces aromatase, increasing estrogen levels Promotes expression of anti-apoptotic proteins, including Mcl-1 Chemotherapy resistance Main regulatory cytokine of hepatic CRP synthesis Predicts response to bevacizumab therapy
TNFα Source: Macrophages [77], ovarian tumor cells, adipocytes	Increased in obesity and DM [74]	Induces MMP production by macrophages, which leads to increased tumor invasiveness [77] Promotes angiogenesis Acts as autocrine and paracrine growth factor for ovarian tumor cells Decreases adiponectin production Induces expression of aromatase in adipose tissue
Leptin Source: Adipocytes	Increased in obesity	Reduces anti-tumor cytotoxicity, perforin production, and IFN-γ secretion by NK cells Suppresses Treg differentiation Increases monocyte secretion of IL-6 and TNFα Apoptotic resistance Increased proliferation in ovarian cancer cells Increases cyclin D1 expression Decreased PFS in EOC tumors with increased leptin receptor (Ob-R) expression Facilitates cell migration
Adiponectin Source: Adipocytes	Decreased in obesity Negatively correlated with waist-hip ratio and visceral fat content Decreased in DM	Inhibits TNF-α induced NF-κB signaling Negative regulator of angiogenesis
MCP-1 Source: Ovarian tumor cells [77]	Induced by HIF, which is elevated in obesity	Recruits circulating monocytes to the tumor microenvironment Tumor derived MCP-1 significantly correlates with TAM density in ovarian tumors [77] May play a role in angiogenesis regulation [77]
CRP Source: Liver	Increased in obesity and DM [74]	Elevated CRP associated with increased risk of ovarian cancer