The Influence of Biologically Active Substances Secreted by the Adipose Tissue on Endometrial Cancer

Abstract

Endometrial cancer is one of the most frequently diagnosed gynecological neoplasms in developed countries and its incidence is rising. Usually, it is diagnosed in the early stages of the disease and has a good prognosis; however, in later stages, the rate of recurrence reaches up to 60%. The discrepancy in relapse rates is due to the heterogeneity of the group related to the presence of prognostic factors affecting survival parameters. Increased body weight, diabetes, metabolic disturbances and estrogen imbalance are important factors for the pathogenesis of endometrial cancer. Even though prognostic factors such as histopathological grade, clinical stage, histological type and the presence of estrogen and progesterone receptors are well known in endometrial cancer, the search for novel prognostic biomarkers continues. Adipose tissue is an endocrine organ involved in metabolism, immune response and the production of biologically active substances participating in cell growth and differentiation, angiogenesis, apoptosis and carcinogenesis. In this manuscript, we review the impact of factors secreted by the adipose tissue involved in the regulation of glucose and lipid metabolism (leptin, adiponectin, omentin, vaspin, galectins) and factors responsible for homeostasis maintenance, inflammatory processes, angiogenesis and oxidative stress (IL-1β, 6, 8, TNFα, Vascular endothelial growth factor (VEGF), Fibroblast growth factors (FGFs)) in the diagnosis and prognosis of endometrial cancer.

Adipokines as New Biomarkers of Immune Recovery: Apelin Receptor, RBP4 and ZAG Are Related to CD4+ T-Cell Reconstitution in PLHIV on Suppressive Antiretroviral Therapy

“…Interestingly, both adiponectin and omentin seem to exert both anti-inflammatory and pro-inflammatory effects according to the cell-specific differences in the adiponectin-and omentin-induced secretory process. Indeed, on the one hand, both adiponectin and omentin induce macrophage differentiation towards the M2 phenotype [31] and inhibit the secretion of inflammatory cytokines, such as TNFα and IL-6 [34][35][36][37]. On the other hand, adiponectin and omentin promote the secretion of pro-inflammatory cytokines (e.g., IL-6 [38,39], IL-1, IFNγ [40]) and chemokines (e.g., MIP1α [39]) from activated CD4 + T cells [40] and stimulate the activation of inflammatory pathways, such as NF-kB signaling, or the shift towards the M1 phenotype.…”

Protective Effects of Irbesartan, an Angiotensin Receptor Blocker with PPARγ Agonistic Activity, against Estradiol Benzoate-Induced Endometrial Hyperplasia and Atypia in Female Rats via Modulation of TNFα/Survivin Pathway

“…As mentioned above, the PPARγ-mediated inhibition of EH can be due to a decrease in oxidative stress [ 33 ], inflammation [ 42 ], survivin [ 19 ], and an increase in cleaved caspase 3 [ 17 ]. In addition, PPARγ activation mediates IRB-induced adiponectin upregulation [ 51 ], which was found to be linked with decreased EC risk [ 52 ].…”

The Regulatory Role of Lipid Metabolism in Endometrial Cancer

“…In addition, adiponectin therapy inhibited the phosphorylation of AKT of KLE and HEC-1-A and inhibited the phosphorylation of ERK1/2 by expression and activation of PTEN gene [ 23 ]. Gal-3, Gal-3 in the galactocoagulin gene exists in a and concentration dependent form, and gal-3-induced ERK1/2 expression is also associated with calcium and protein kinase C-related activation [ 24 , 25 ].…”

“…In research studies related to lipid metabolism in endometrial cancer, omentin, an adipokine secreted from visceral fat, stimulates apoptosis by activating the JAK signaling pathway and p53 upregulation mechanism [ 25 ]. Leptin regulates PI3K/AKT3 and ERK1/2 signaling through the JAK/STAT pathway and increases the expression of anti-apoptotic proteins such as XIAAP and systemic inflammation factors (TNF- α , IL6).…”