Abstract 795: The capacity of high-grade serous ovarian cancer cells to form spontaneous multicellular structures (SMCS)in vitropredicts theirin vivotumorigenicity
Authors: Alicia A. Goyeneche, Zu-hua Gao, Carlos M. Telleria
Journal: Cancer Research (2017)

Abstract High grade serous ovarian cancer (HGSOC) is the most frequent histopathological subtype among epithelial ovarian cancers (OC). While an increase in concentration of CA125 in the blood anticipates clinical remission following standard of care, we lack biomarker/s to diagnose early disease stage or predict progression speed. In this work we question whether the capacity of HGSOC cells to form Spontaneous Multi-Cellular Structures (SMCS) when incubated under culture conditions that promote, not prevent, adherence to a plastic surface, correlates with their degree of tumorigenicity. We studied 3 HGSOC cell lines developed from the same patient’s ascites: longitudinally along disease progression—established at platinum-sensitive relapse (PEO1); from further progressive disease 10 months (mo.) later (PEO4); and after failure to respond to high-dose cisplatin 3 mo. later (PEO6). We noticed all cell types developed an adherent phenotype and a differential capacity to form SMCS. This capacity was more evident in PEO6 cells having high SMCS forming ability, followed by PEO4 cells denoting some SMCS forming capacity, while PEO1 cells depicted no apparent capability to form SMCS. Next, 2x106 PEO1, PEO4 or PEO6 cells were implanted into the abdominal cavity of nude mice; the animals were sacrificed either after having met an end-of-wellness endpoint criterion, or after a maximum of 14 mo. if no such criteria were met. PEO6-injected mice reached the humane endpoint due to accumulation of ascites 6-7 mo. following injection, and presented discrete yet visible solid tumors in the omentum, pancreatic-spleen region, liver base and diaphragm. Animals injected with PEO4 or PEO1 cells, however, did not develop any apparent disease 14 mo. following injection. Yet, when a 10-fold higher load of PEO4 cells but not PEO1 cells (i.e., 20x106) were injected, animals met euthanasia criteria due to ascites accumulation 6 mo. later and displayed macroscopic disease similar to that caused by 1/10 of the load of their successors (PEO6 cells) within the same timeframe. Furthermore, the anatomical localization and histopathological aspect of the lesions generated with PEO6 cells were similar from that generated with PEO4 cells, suggesting that the more aggressive PEO6 cells were likely present, although in fewer quantities, within the less aggressive PEO4 cell population. Our data demonstrate, then, that the in vitro SMCS forming capacity of HGSOC cells has a positive correlation to their capacity to sicken the animals. Moreover, this study suggests that the in vitro SMCS forming capacity of epithelial OC cells obtained from ascites of patients diagnosed with HGSOC may be used to predict their aggressiveness and, consequently, guide prognosis. Citation Format: Alicia A. Goyeneche, Zu-hua Gao, Carlos M. Telleria. The capacity of high-grade serous ovarian cancer cells to form spontaneous multicellular structures (SMCS) in vitro predicts their in vivo tumorigenicity [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 795. doi:10.1158/1538-7445.AM2017-795