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Updated: Aug 11, 2026
Ex Vivo Culture of Primary Human Fallopian Tube Epithelial Cells
Published on: May 9, 2011
Targeting of free fatty acid receptor 1 in EOC: A novel strategy to restrict the adipocyte-EOC dependence
Adnan Munkarah1, Ismail Mert2, Jasdeep Chhina3
1Department of Women's Health, Obstetrics and Gynecology, Henry Ford Hospital, USA; Josephine Ford Cancer Institute, Henry Ford Hospital, Detroit, MI, USA.
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.
Insights
Free fatty acids (FFA) fuel ovarian cancer growth. Targeting FFAR1/GPR40, a receptor activated by FFA, may offer a new therapeutic strategy for epithelial ovarian cancer (EOC).
Area of Science:
- Oncology
- Molecular Biology
- Metabolism
Background:
- Adipocyte-derived free fatty acids (FFA) are known to fuel epithelial ovarian cancer (EOC) cell energy demands.
- FFA may also influence EOC progression through specific signaling pathways.
- G-protein coupled receptors (GPCRs) activated by FFA (FFAR/GPCRs) have been recently identified.
Purpose of the Study:
- To investigate the role of FFAR/GPCRs in epithelial ovarian cancer (EOC).
- To assess FFAR/GPCRs as potential therapeutic targets for EOC treatment.
Main Methods:
- Examined mRNA expression of FFAR/GPCR family members (FFAR1/GPR40, FFAR2/GPR43, FFAR3/GPR41, FFAR4/GPR120, GPR84) using RT-PCR.
- Utilized a syngeneic mouse model of EOC on high-fat or regular diets.
- Analyzed EOC cell lines exposed to FFAs and patient tumor specimens.
- Assayed cell survival and energy metabolism using MTT assays following inhibition of FFAR1/GPR40 with GW1100.
Main Results:
- High-grade serous carcinoma specimens showed significantly increased GPR40 expression compared to normal ovaries (p=0.0020), with higher expression in advanced stages.
- Ovarian tumors in mice fed a high-fat diet exhibited elevated GPR40 expression.
- Exposure of EOC cells to FFAs increased GPR40 expression.
- Inhibition of FFAR1/GPR40 with GW100 led to growth inhibition and altered energy metabolism in EOC cell lines.
Conclusions:
- FFA-induced EOC cell growth may be partly mediated by FFAR1/GPR40.
- Targeting FFAR1/GPR40 represents a promising therapeutic strategy for EOC.
- This approach may offer a targeted treatment option for a specific subset of EOC patients.
