Abstract B35: An innovative in vivo model of metastasizing prostate cancer using orthotopic xenografts

Abstract

Abstract Introduction: In this study, we aimed to develop a versatile in vivo model of prostate cancer using orthotopic xenografts, which adequately represents intraprostatic tumor growth as well as the natural routes of metastatic spread. Materials and Methods: 5x105 VCaP-, LuCaP136-, and LuCaP147 cells were injected into the prostate of male CB17-SCID mice (n=8 for each cell line; VCaP cultured as monolayer, LuCaP136 and LuCaP147 as three-dimensional spheroid culture). During 12 weeks of follow-up, orthotopic tumor growth and the development of metastases was monitored by repetitive serum-PSA measurements and imaging studies (ultrasonography, CT, MRI). At autopsy, primary tumors and metastases were harvested and examined by conventional histology (H&E) and immunohistochemistry (CK5, CK8, AMACR, AR, Ki67, ERG, PSA). From the results of the imaging studies and PSA measurements, tumor volume doubling time, tumor-specific growth rate, and PSA-density were calculated for each cell line. Results: All 24 mice developed orthotopic tumors, whose growth could be reliably monitored by ultrasonography, CT, MRI, and serum-PSA measurements. 4 animals died during follow-up (1 in the VCaP group, 1 in the LuCaP136 group, 2 in the LuCaP147 group). Mean PSA-density was 433.9 ng/ml per ml tumor in the VCaP group, 6.5 ng/ml per ml tumor in the LuCaP136 group, and 11.2 ng/ml per ml tumor in the LuCaP147 group. Tumor-specific growth rate and tumor volume doubling time were 3.87% per day and 21.24 days in the VCaP group, 3.11% and 27.57 days in the LuCaP136 group, and 4.47% and 16.2 days in the LuCaP147 group, respectively. In up to 100% of animals, lymph node metastases could be detected after 12 weeks (5/7 in the VCaP group, 6/7 in the LuCaP136 group, 6/6 in the LuCaP147 group). These could also be visualized by ultrasonography and MRI. Immunohistochemistry showed positive CK8, AR, and AMACR as well as negative CK5 reactions in all tumors. ERG-straining was positive in VCaP and negative in both LuCaP tumors, Ki67 proliferation indices were >90% in all groups. Conclusions: By using different monolayer as well as 3D spheroid cell cultures in an orthotopic xenograft model, we could establish an innovative, versatile in vivo model of prostate cancer, which enables the study of both intraprostatic tumor growth as well as metastatic spread to regional lymph nodes. Citation Format: Johannes Linxweiler, Christina Körbel, Andreas Müller, Markus Hammer, Michael Stöckle, Kerstin Junker, Michael D. Menger. An innovative in vivo model of metastasizing prostate cancer using orthotopic xenografts [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr B35.