Abstract 5178: Ascites conditioning reduces latency in vivo for progression of ID8 TP53 KO murine ovarian cancer model
Authors: Taylor Barnhisel, Zari Dehdashti, Stephen Kron
Journal: Cancer Research (2025)

High-grade serous ovarian carcinoma (HGSOC), an aggressive subtype of epithelial ovarian cancer (EOC) characterized by peritoneal metastasis at diagnosis and poor prognosis, is almost universally associated with p53 mutations. Mouse models of EOC and particularly HGSOC remain unsatisfactory for therapy development. Underscoring its low-grade behavior, intraperitoneal injection of the C57BL/6-derived EOC cell line ID8 from tissue culture is followed by a 9-to-10-week latency before onset of peritoneal carcinomatosis, associated with development of ascites and abdominal distention. Toward overcoming limitations of ID8 cells as a mouse model for HGSOC, Walton et al. (2018) performed CRISPR/Cas9-mediated knockout and isolated the F3 Trp53-/- cell line. While the latency period was reduced upon Trp53 deletion, 5-to-6-weeks may pass before ascites can be observed after injection of plastic-grown F3 cells. Prior studies have ascribed the delay to a dearth of cancer stem cells and/or a low propensity for colonizing the omentum. Indeed, ID8 cells isolated after 11 or 12 weeks from ascites fluid were found to be enriched for stem cells and to display immediate omental colonization and ascites onset. We confirmed that transplanting even small volumes of F3 ascites fluid into naive mice led to rapid carcinomatosis and ascites. Strikingly, passaging F3 ascites cells in tissue culture did not restore latency. These observations suggested that ascites-derived Trp53-/- ID8 cells might provide superior HGSOC models. To form an ascites-conditioned F3 cell line, CF3, plastic-grown F3 cells were injected into a C57BL/6 mouse, allowed to progress to carcinomatosis and ascites, and the ascites cells isolated and passaged four to six times. Within 14 days after being injected with CF3 cells, mice display ascites. Examining the viscera reveals visible tumors studding the abdominal mesentery and omentum. At this timepoint, mice injected with F3 display no visible signs of engraftment. CF3-injected mice reach a humane endpoint within approximately 30 days, compared to about 54 days for F3. Underlining the primary effect of ascites conditioning as reduced latency, CF3 and F3 mice display similar ascites volume, size, and distribution of metastases at their endpoints. Despite the rapid onset of carcinomatosis, CF3 cells maintain similar sensitivity to carboplatin in vivo. We suggest that ascites-conditioned cells provide a rapid and robust preclinical HGSOC model that may streamline experimental timelines and facilitate evaluation of immune and other therapies. Supported by Roswell Park-University of Chicago Ovarian Cancer SPORE P50 CA159981 and the University of Chicago Medicine Comprehensive Cancer Center. Citation Format: Taylor Barnhisel, Zari Dehdashti, Stephen Kron. Ascites conditioning reduces latency in vivo for progression of ID8 TP53 KO murine ovarian cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5178.