The Contribution of Adipocyte Reservoirs Towards Ovarian Cancer Growth in Time and Site-Specific Manner
Hijaz M, Raja V, Sakr S, Buekers TE, Morris RT, Giri S, Munkarah AR, and Rattan R. The Contribution of Adipocyte Reservoirs Towards Ovarian Cancer Growth in Time and Site-Specific Manner. Gynecol Oncol 2019; 154:67-68.
Objective: Free fatty acids derived from omentum adipocytes have been shown to meet the energy demands of rapidly proliferating epithelial ovarian cancer (EOC) cells. We have previously shown that EOC progresses aggressively in high-fat diet (HFD)-fed obese mice, highlighting the importance of overall adipocyte reserves in promoting EOC progression. Since major adipose reservoirs exist at multiple body sites (omental, retroperitoneal, subcutaneous, visceral, and gonadal), the aim of the study is to determine the contribution of individual adipocyte reserves in promoting EOC growth in time and site-specific manner. Method: Eighty female B6 mice were fed either HFD or a regular diet (RD). Post 5 weeks, mouse EOC ID8 (5 million cells/mouse) was injected intraperitoneally. Tumor growth was monitored by in situ luciferases-guided imaging. Sets of mice were sacrificed at days 0, 20, 40, and 60. Individual adipocyte reserves were isolated, weighed, and processed for microscopic analysis. Results: The HFD-fed mice displayed increased EOC burden compared to RD-fed mice (P < 0.001). The starting ratio of total adipose to body weight was higher in HFD mice compared to RD mice (P < 0.01) but declined with time as tumor progressed. The decline in adipose/body weight ratio was more pronounced in HFD mice than in RD mice at every timepoint studied. Individual microscopic analysis of each adipose reserve (omental, retroperitoneal, subcutaneous, visceral, and gonadal) revealed the HFD group lost more adipose mass at each site compared to RD mice, even at the early timepoint of 20 days (P < 0.01). Conclusion: Our study suggests that EOC cells can acquire free fatty acids from various host adipocyte reserves, regardless of the location. In addition, the presence of excess adiposity may be a crucial factor in the mechanism of proliferation and spread of EOC.