Expression of short chain fatty acid receptors in human prostate cancer: Role in tumor cell survival and motility.

B73

Genetic, epigenetic, and environmental factors influence tumor development and progression. Environmental factors, such as exposure to radiation and carcinogens, increase the risk of cancer by causing genetic mutations. A lesser understood, but widely implicated, risk factor for cancer is certain lifestyles related to diet. Short chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are relatively high in caloric content and its levels of SCFAs in blood and other parts of the body can be influenced by diet such as alcohol consumption and by infections. Recently, two orphan G-protein coupled receptors, GPR41 and GPR43, have been identified as novel receptors for SCFAs, with propionate as the most potent agonist. Through RT-PCR and immunocytochemistry, we demonstrated that prostate cancer cells expressed GPR43, and to much less extent, GPR41. Immunohistochemical staining for GPR43 indicated that most normal prostate glands showed focal and weak staining. Increased expression was observed in high grade prostatic intraepithelial neoplasia. Most prostatic adenocarcinoma showed variable cytoplasmic staining. Higher expression of GPR43 was noted in some high grade tumors. Treatment of PC-3 or LNCaP cells with SCFAs, especially propionate, suppressed apoptosis and promoted survival of prostate cancer cells in the absence of serum trophic factors. Further, we found that SCFAs decreased the adhesion of prostate cancer cells toward fibronectin and stimulated the migration of prostate cancer cells under serum free conditions. Our data suggest that prostate cancer cells express a novel membrane receptor for SCFAs and that SCFAs exert pleiotrophic effects on prostate tumor cell survival, adhesion, and motility.