Abstract 1979: Cell lines that genomically resemble high-grade serous ovarian carcinomas display differences in growth and invasive capacities in an orthometastatic nude mouse model
Authors: Alghamdi Sarah S. , Goyeneche Alicia A. , Gao Zu-hua , Telleria Carlos M. 
Published: July 2017

Ovarian cancer (OC) is a complex disease that can be divided into various histopathological subtypes. High-grade serous OC (HGSOC) is the most abundant histotype, accounting for up to 70% of all OC cases. Whereas the majority of patients are diagnosed when the disease is already disseminated in the peritoneal cavity, orthometastatic mouse models of peritoneal OC—needed to perform preclinical studies—are not well developed. The human OC cell lines mostly studied for in vivo tumor development in immunosuppressed mice have been implanted subcutaneously, not intra-abdominally, thus not reflecting the tumor niche this disease actually encounters when advanced. Furthermore, most studies utilize cells which do not have the genetic fidelity of HGSOC. Thus, we set up a study to track the development of intra-abdominal disease induced by 3 human OC cells lines with the genetic fidelity of HGSOC: OVCAR-4, OVSAHO, and PEO14. The 3 cell lines showed abundant expression of ARID1A, PAX8 and mutant p53, with varied levels of expression of CA125 and WT1. We contrasted among them, the time needed for the disease to develop, the tissues being targeted, and the histopathological abnormalities detected. We found that the elapsed time for the disease to develop for the 3 lines ranged between 4 to 11 months. This result stands in stark contrast with the less than 3 months it takes for the disease to evolve in the peritoneal cavity when injecting cells of unlikely HGSOC genomic fidelity, such as SKOV-3, IGROV-1, or A2780. Within the cell lines with HGSOC genotype we found commonalities and differences in terms of their in vivo behavior. Among the commonalities, all cells homed to the omental-spleen-pancreatic area, the liver base, the mesentery, and the diaphragm. Among the differences, PEO14 cells developed into sizable masses not invading the parenchyma of the abdominal organs. OVSAHO cells developed discrete masses closely surrounding the organs, while OVCAR-4 cells displayed full invasiveness into the parenchyma of several abdominal organs in addition to developing micro-metastases within the lung stroma. Whereas OVCAR-4 cells caused accumulation of large volume bloody ascites carrying abundant multicellular structures (MCS), OVSAHO and PEO14 cells led to the formation of low volume bloody ascites carrying scarce MCS. These phenotypic heterogeneities were further reflected in the different end-of-wellness endpoints criteria reached, which were: the increase in the abdominal circumference caused by the accumulation of ascites in animals carrying OVCAR-4 cells, the size of the solid abdominal masses in animals carrying PEO14 cells, and the dramatic weight loss in animals carrying OVSAHO cells. In conclusion, we show that, despite having similar genetic fidelities, HGSOC cell lines are heterogeneous in terms of their phenotypic behavior when ortometastatically implanted in nude mice.

Citation Format: Sarah S. Alghamdi, Alicia A. Goyeneche, Zu-hua Gao, Carlos M. Telleria. Cell lines that genomically resemble high-grade serous ovarian carcinomas display differences in growth and invasive capacities in an orthometastatic nude mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1979. doi:10.1158/1538-7445.AM2017-1979