Abstract 325: Characterization and evaluation of a mouse ovarian cancer model for its preclinical suitability.

Abstract

Abstract Ovarian cancer is the second most frequent invasive malignancy of the female genital tract and the most common cause of death among women with gynecologic malignancies. Although epithelial ovarian cancer (EOC) accounts for over 90% of all ovarian malignancies, the lack of proper animal models that mimic the development and consequences of human EOC limits the ability of current preclinical ovarian cancer models to predict treatment response. The orthotopic development of syngeneic EOC within its relevant tumor microenvironment is an experimental ideal. Here, we demonstrate the development and characterization of a syngeneic EOC mouse model in immunecompetent C57BL/6 mice by orthotopic implantation of ID 8 mouse ovarian cancer cells. Using conventional and ultrasound-based techniques to compare tumor weight, volume and vascularity we followed the development of primary tumors, metastases and ascites over 16 weeks. ID 8 cells were implanted directly underneath the left ovarian bursa. Normal saline was injected to the contralateral ovary as control. Ovarian tumors grew consistently throughout the study period; ovarian weight and volume increased twelve and seven fold, respectively, compared to the contralateral, non-cancerous ovary. Ultrasound measurements of primary tumors and surrounding tumor tissue correlated with the actual size after surgical tumor harvest. Abdominal ascites were first observed at 12 weeks post orthotopic ID8 implantation with volume changes correlating with changes in abdominal circumference. Metastatic lesions were identified by ultrasound at 12 weeks after orthotopic ID8 implantation; sites included peritoneum, liver, and intestine. Histopathological analysis of tumors and metastases indicated similarities between orthotopic ID8 ovarian tumors and human ovarian tumors, except a significantly lower formation of angiogenic vasculature within the ID8 tumors. This study confirms the successful development of a mouse model that closely replicates characteristics seen in human ovarian cancer patients. It shows the feasibility of using ultrasound to assess tumor formation, progression and vascularization. Furthermore, we demonstrate potential shortcomings, which could significantly limit the use of current animal models predicting therapeutic efficacy of novel agents, especially anti-angiogenic therapeutics, impacting the translation of preclinical information to actual clinical outcomes. Citation Format: Sungpil Cho, Yongen Sun, Andrew P. Soisson, Mark K. Dodson, C. Matthew Peterson, Elke A. Jarboe, Anne M. Kennedy, Margit M. Janat-Amsbury. Characterization and evaluation of a mouse ovarian cancer model for its preclinical suitability. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 325. doi:10.1158/1538-7445.AM2013-325