Ablation of hematopoietic stem cell derived adipocytes reduces tumor burden in syngeneic mouse models of high-grade serous carcinoma

Abstract

Hematopoietic stem cell-derived adipocytes (HSCDAs) are an adipocyte subtype derived from myeloid precursors. We hypothesized that HSCDAs promote high-grade serous ovarian carcinoma (HGSC). Despite similar adipogenic differentiation, primary human female HSCDAs exhibit transcriptional differences from conventional mesenchymal adipocytes (CMAs), including upregulation of metabolic pathways. HSCDAs secreted greater amounts of IL-6 and IL-8 than CMAs. We generated immunocompetent HSCDA Proficient (HSCDA-Pro; can make both adipocyte subtypes) and Deficient (HSCDA-Def; can only make CMAs) mice and conducted two independent tumor studies using two unique syngeneic HGSC models. Tumor burden trended lower in HSCDA-Def mice in both models. Omentum tumors from HSCDA-Def mice exhibited downregulated transcription of metabolic pathways. Tumors from HSCDA-Def mice also had lower densities of dendritic cells (DC) and natural killer (NK) cells. These data suggest that HSCDAs promote HGSC progression through metabolic and immune pathways.