Abstract 4962: Derivation of bone trophic human prostate cancer cells

Abstract

Abstract Introduction: Bone metastases continue to be the main source of morbidity and mortality in prostate cancer patients. Determining the mechanism(s) by which prostate cancer cells utilize the bone microenvironment to survive and grow is key to developing strategies to prevent metastasis. Such approaches could affect disease morbidity and mortality, as nearly 80% patients have bone metastases at the time of death. The finding that disseminated cancer cells can be detected in 72% of patients prior to prostatectomy led to the realization that prostate cancer cells disseminate early and persist in the bone for extended periods of time prior to detection. This may be due to factors within the metastatic microenvironment that restrict cancer cell growth. Unfortunately, current models of prostate cancer bone metastases are lacking, and the field would greatly benefit from the creation of new bone trophic model cell lines. Hypothesis: We hypothesize that the AR positive, human CWR22Rv1 can be made bone trophic by serial passage through mice in an experimental metastasis assay. Methods: CWR22Rv1 cells were engineered to express the synthetic firefly luciferase luc 2, and injected into the left ventricle of intact male, 8 week old NOD/SCID mice. Metastatic growth was assessed weekly, and metastases were examined histologically at the experimental endpoint. Bone metastatic cells were extracted, cultured and ultimately re-injected to select for a sub-population of bone trophic human prostate cancer cells. Results: CWR22Rv1 cells lodge in the skeleton where they persist for approximately two weeks. The cells then undergo progressive growth (as indicated by increasing signal intensity), culminating in overt metastases at the experimental endpoint (8 weeks post injection). The 145-fold increase in luciferase signal was accompanied by osteoblastic-lesions in the skeleton, most notably calvarial lesions. Several animals developed additional metastases in the hind limbs. Cells that were passaged once or twice through animals exhibit increased bone tropism, but are not simply more metastatic as indicated by whole body luciferase signal. Conclusions: Passage through animals is successfully generating bone trophic human prostate cancer cells. These baseline data serves as a staring point for additional studies to more precisely define the kinetics of metastatic growth in this model system. Future work will identify molecular changes that occur in the prostate cancer cells and the bone microenvironment both during and prior to metastatic outgrowth. Note: This abstract was not presented at the meeting. Citation Format: Erin N. Howe, Ryan M. Brown, Russell Z. Szmulewitz, Carrie W. Rinker-Schaeffer. Derivation of bone trophic human prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4962. doi:10.1158/1538-7445.AM2014-4962