Abstract B43: Xenograft mouse models for ovarian cancer
Authors: Lamminen Tarja , Kaipio Katja , Mikkonen Piia , Roering Pia , Carpén Olli 
Published: August 2014

Ovarian cancer is the most lethal gynecologic malignancy in developed countries. The incidence is 1 in 70 women, and 5-year survival rate below 50 %. Although major achievements have been reached in understanding the molecular alterations underlying the disease, the discoveries need yet to be integrated into clinical practice. A major obstacle in this process may be the translation of in vitro findings into diagnostic tests and novel therapeutic approaches. Well-characterized and representative preclinical mouse models that recapitulate the heterogeneity of tumors in patients are crucial in narrowing the gap between experimental and clinical studies. The aim of this work was to test and validate various mouse xenograft models for their applicability in ovarian cancer research.

We tested several xenograft mouse models using (1) established commercially available ovarian cancer cell lines, (2) primary cell lines originating from high grade serous ovarian cancers or ascitic fluid, and (3) primary or metastatic tumor tissue directly from operation. Cell growth, tumor take rate and histopathological correlation between mouse and human tumors were applied for selection of commercial cell lines in xenograft experiments into athymic nude mice. Intrabursal orthotopic inoculations were used to model early, and intraperitoneal inoculations to model late stage ovarian cancer. Translational aspects were studied by comparing the histopathology between mouse tumors and human ovarian cancer specimens and by testing the utility of serum biomarkers CA-125 and HE-4 in mouse models. The mouse xenograft models faithfully represented the morphology of human serous ovarian cancer and many of the tissue markers were similarly expressed in human and mouse tumors. Importantly, the serum biomarker analysis developed in this study allowed follow-up of the tumor burden ex vivo. Such biomarker will be useful in studying drug responses and other tumor modifying therapies.

The primary cell lines were inoculated subcutaneously to immunodeficient NOD-SCID and NOG mice in order to enrich and characterize ovarian cancer initiating cells (OCICs). Due to the low rate of tumor formation of in vitro cultured OCICs, we have started to use patient derived tumor xenograft (PDTX) transplantations. In this model fresh surgical tissue, sectioned in app. 3 mm3 pieces are implanted into the flanks of immunodeficient NOG mice. The preliminary results show a take rate of 75 % with PDTXs. Histopathological comparisons of original human specimen to mouse tumors reveals that this model also recapitulates the human microenvironment in PDTX modelling. Also, the PDTX model appears to increase the probability for successfully establishing novel primary cell lines.

In conclusion, mouse xenograft models offer translational and important validation methods for pre-clinical cancer drug development and diagnostics.

Citation Format: Tarja Lamminen, Katja Kaipio, Piia Mikkonen, Pia Roering, Olli Carpén. Xenograft mouse models for ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr B43.