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Updated: Jan 19, 2026
Enrichment for Chemoresistant Ovarian Cancer Stem Cells from Human Cell Lines
Published on: September 10, 2014
Adipocytes promote ovarian cancer chemoresistance
Jiang Yang1,2,3, Munir M Zaman4, Iliyan Vlasakov5
1Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, MA, 02115, USA.
Abstract:
Ovarian cancer (OvCa), while accounting for only 3% of all women's cancer, is the fifth leading cause of cancer death among women. One of the most significant obstacles to successful OvCa treatment is chemoresistance. The current lack of understanding of the driving mechanisms underlying chemoresistance hinders the development of effective therapeutics against this obstacle. Adipocytes are key components of the OvCa microenvironment and have been shown to be involved in OvCa cell proliferation, however, little is known about their impact on OvCa chemoresistance. In the current study, we found that adipocytes, of both subcutaneous and visceral origin, secrete factors that enhance the resistance of OvCa cells against chemotherapeutic drugs by activating the Akt pathway. Importantly, we have demonstrated that secreted lipids mediate adipocyte-induced chemoresistance. Through a comprehensive lipidomic analysis, we have identified this chemo-protective lipid mediator as arachidonic acid (AA). AA acts on OvCa cells directly, not through its downstream derivatives such as prostaglandins, to activate Akt and inhibit cisplatin-induced apoptosis. Taken together, our study has identified adipocytes and their secreted AA as important mediators of OvCa chemoresistance. Strategies that block the production of AA from adipocytes or block its anti-apoptotic function may potentially inhibit chemoresistance in OvCa patients.
Insights
Adipocytes promote ovarian cancer chemoresistance by secreting arachidonic acid (AA), which activates the Akt pathway and prevents apoptosis. Blocking AA may offer new ovarian cancer treatment strategies.
Area of Science:
- Oncology
- Cancer Biology
- Molecular Medicine
Background:
- Ovarian cancer (OvCa) is a leading cause of cancer death in women.
- Chemoresistance remains a major challenge in effective OvCa treatment.
- The role of adipocytes in OvCa chemoresistance is not well understood.
Purpose of the Study:
- To investigate the impact of adipocytes on chemoresistance in ovarian cancer.
- To identify the mechanisms by which adipocytes influence OvCa cell response to chemotherapy.
- To determine the role of secreted factors, particularly lipids, in adipocyte-mediated chemoresistance.
Main Methods:
- Co-culture of ovarian cancer cells with adipocytes (subcutaneous and visceral).
- Assessment of OvCa cell resistance to chemotherapeutic drugs.
- Analysis of signaling pathways, including the Akt pathway.
- Comprehensive lipidomic analysis to identify key lipid mediators.
- Direct testing of identified lipid mediators on OvCa cells and apoptosis.
Main Results:
- Adipocytes enhance OvCa cell resistance to chemotherapy by activating the Akt pathway.
- Secreted lipids from adipocytes mediate this chemoresistance.
- Arachidonic acid (AA) was identified as the specific lipid mediator.
- AA directly activates Akt in OvCa cells, inhibiting cisplatin-induced apoptosis.
- AA's effect is independent of its downstream metabolites like prostaglandins.
Conclusions:
- Adipocytes and their secreted arachidonic acid (AA) are significant mediators of ovarian cancer chemoresistance.
- AA promotes OvCa cell survival by activating the Akt pathway and inhibiting apoptosis.
- Targeting AA production or its anti-apoptotic function presents a potential therapeutic strategy for overcoming chemoresistance in ovarian cancer.
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