Elucidation of CXCR4‐CXCL12 mediated angiogenesis mechanism in endometriosis

Abstract

Endometriosis is defined as the presence of the endometrial tissue outside of the uterine cavity, primarily on the pelvic peritoneum, and ovaries. The main symptoms are chronic pelvic pain, pain during intercourse, and infertility. High CXCR4 mRNA levels were reported in endometriotic lesions in a rat model of endometriosis and protein expression is higher in human endometriosis tissues compared to control endometrium. CXCR4 is a G‐protein coupled receptor, activated by its specific ligand, chemokine stromal cell‐derived factor (CXCL12). CXCR4 is predominantly expressed by endometrial epithelial cells (EEC) and its ligand, CXCL12, by endometrial stromal cells. The CXCR4‐ CXCL12 axis is a potent inducer of angiogenesis, migration/invasion and cell proliferation. It has been shown that the CXCR4‐CXCL12 axis can induce angiogenesis by inducing expression of vascular endothelial growth factor (VEGF). We hypothesize that CXCL12 can induce the expression of VEGF and its receptors, (VEGFR1 and VEGFR2) in EEC. The aim of this study is to determine if CXCL12 induce the expression of the angiogenic factors, VEGF and its receptors, in EEC. Cells were incubated with hrCXCL12α, and the expression of VEGF and its receptors was assessed by ELISA and Western blot, respectively. Preliminary results showed that EEC only expresses VEGFR1. We expect to determine the effects of CXCL12 in the expression of the angiogenic factors studied in EEC and endometriotic epithelial cells. Our findings may have implications for future therapeutical strategies that may target the angiogenic components of endometriosis. R25GM096955, 1R25‐GM082406