The prostaglandin F(2alpha) (PGF(2alpha)) receptor (FP) is elevated in 
endometrial adenocarcinoma. This study found that PGF(2alpha) signaling via FP 
regulates expression of chemokine (C-X-C motif) ligand 1 (CXCL1) in endometrial 
adenocarcinoma cells. Expression of CXCL1 and its receptor, CXCR2, are elevated 
in cancer tissue compared with normal endometrium and localized to glandular 
epithelium, endothelium, and stroma. Treatment of Ishikawa cells stably 
transfected with the FP receptor (FPS cells) with 100 nmol/L PGF(2alpha) 
increased CXCL1 promoter activity, mRNA, and protein expression, and these 
effects were abolished by cotreatment of cells with FP antagonist or chemical 
inhibitors of Gq, epidermal growth factor receptor, and extracellular 
signal-regulated kinase. Similarly, CXCL1 was elevated in response to 100 nmol/L 
PGF(2alpha) in endometrial adenocarcinoma explant tissue. CXCL1 is a potent 
neutrophil chemoattractant. The expression of CXCR2 colocalized to neutrophils 
in endometrial adenocarcinoma and increased neutrophils were present in 
endometrial adenocarcinoma compared with normal endometrium. Conditioned media 
from PGF(2alpha)-treated FPS cells stimulated neutrophil chemotaxis, which could 
be abolished by CXCL1 protein immunoneutralization of the conditioned media or 
antagonism of CXCR2. Finally, xenograft tumors in nude mice arising from 
inoculation with FPS cells showed increased neutrophil infiltration compared 
with tumors arising from wild-type cells or following treatment of mice bearing 
FPS tumors with CXCL1-neutralizing antibody. In conclusion, our results show a 
novel PGF(2alpha)-FP pathway that may regulate the inflammatory microenvironment 
in endometrial adenocarcinoma via neutrophil chemotaxis.