CXCL12α induces proliferation and migration of endometrial epithelial cells expressing CXCR4

Endometriosis defined as the presence of endometrial stroma and glands outside the uterus, is associated with chronic pain, inflammation, and increased levels of chemokines. We reported high CXCR4 mRNA levels in endometriotic lesions in a rat model and protein expression in human endometriosis tissues vs. control endometrium. CXCR4 is predominantly expressed by endometrial epithelial cells (EEC) and its ligand CXCL12 by endometrial stromal cells. The CXCR4‐CXCL12 axis plays roles in angiogenesis, invasion, and cell proliferation. We hypothesized that CXCL12α may induce proliferation and migration in EEC expressing CXCR4 via activation of the PI3K/Akt pathway. Cell proliferation and migration of EEC treated with CXCL12α was analyzed by BrdU proliferation and wound healing assays, respectively. We also studied CXCL12α‐mediated induction of Akt phosphorylation by immunoblotting. CXCL12α increased proliferation and migration of EEC vs. media (p<0.05). In addition CXCL12α induced rapid and transient Akt phosphorylation. These data suggest that the CXCR4‐CXCL12α axis can be activated in endometrial cells to promote cell proliferation and migration. These biological functions have been previously shown to be dysregulated in endometriosis, by still undefined mechanisms, leading to survival and growth of ectopic endometrium. R01‐ HD050509 , S06‐GM08239, 1R25‐ GM082406 , R25GM096955‐01