Targeting of free fatty acid receptor 1 in EOC: A novel strategy to restrict the adipocyte-EOC dependence
| Autor: | Adnan R. Munkarah, Jasdeep Chhina, Ismail Mert, Shailendra Giri, S. Hensley Alford, Ramandeep Rattan, Suhail Hamid, Miriana Hijaz, Laila M. Poisson |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
endocrine system endocrine system diseases Carcinoma Ovarian Epithelial Receptors G-Protein-Coupled Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Free fatty acid receptor 1 Adipocyte Adipocytes Animals Humans Medicine Neoplasms Glandular and Epithelial Receptor Ovarian Neoplasms business.industry Obstetrics and Gynecology GPR120 female genital diseases and pregnancy complications Serous fluid 030104 developmental biology Oncology chemistry Biochemistry 030220 oncology & carcinogenesis Cancer cell Cancer research Female Growth inhibition Signal transduction Energy Metabolism business Glycolysis |
| Zdroj: | Gynecologic Oncology. 141:72-79 |
| ISSN: | 0090-8258 |
| DOI: | 10.1016/j.ygyno.2016.02.026 |
| Popis: | Objectives Adipocyte derived free fatty acids (FFA) promote epithelial ovarian cancer (EOC) by acting as a fuel source to support the energy requirement of the cancer cells. FFA may also exert biological effects through signaling pathways. Recently, a family of FFA activated G-protein coupled receptors (FFAR/GPCRs) was identified. Our objective was to investigate the role of FFAR/GPCRs in EOC and assess their potential as therapeutic targets. Methods The mRNA (RT-PCR) expression of FFAR/GPCR family members (FFAR1/GPR40; FFAR2/GPR43, FFAR3/GPR41, FFAR4/GPR120 and GPR84) was examined in: (1) a syngeneic mouse model of EOC fed high energy diet (60% fat) or regular diet (30% fat), (2) EOC cell lines exposed to free fatty acids and (3) specimens from 13 histologically normal ovaries and 28 high grade ovarian serous carcinomas. The GPR 40 antagonist, GW1100, was used to inhibit FFAR1/GPR40 and cell survival was assayed by MTT in various cell lines. Results High Grade Serous carcinoma specimens expressed significantly increased GPR40 compared to normal ovaries ( p =0.0020). Higher expression was noted in advanced stage disease. ID8 ovarian tumors from mice fed with high fat diet also showed higher GPR40 expression. Exposing EOC cells to FFAs, increased GPR40 expression. Treatment of EOC cell lines with GW100 resulted in growth inhibition and was associated with an alteration in their energy metabolism. Conclusion FFA-induced cancer cell growth may be partly mediated through FFAR1/GPR40. Targeting of FFAR1/GPR40 may be an attractive treatment strategy in EOC, and possibly offers a targeted treatment for a subset of EOC patients. |
| Databáze: | OpenAIRE |
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