In developed countries, prostate cancer (PCa) is the most prevalent cancer and the second most common cause of cancer related death in males. Tumors from patients exhibiting disease progression after systemic androgen deprivation treatment (ADT), referred to as castration resistant prostate cancer (CRPC), often show differentiation towards an aggressive phenotype neuroendocrine prostate cancer or NE-PC. In our study, we used the Simian-Virus 40 (SV-40) T-antigen driven model of the mouse prostate (TRAMP) as a model for studying carcinogenesis of NE-PC on a cellular level. By isolation of cell populations of both basal and non-basal compartments of the murine prostate epithelium using flow cytometry (FACS), we traced down the roots of neuroendocrine differentiation in TRAMP mice: When successfully engrafted subcutaneously in NSG mice or grown as spheroids in vitro, non-basal cells harboring upregulation of neuroendocrine markers showed growth advantages when compared to cells of the basal cell compartment. Further, by means of RNA sequencing, we found potential novel therapeutical targets and biomarkers for these cells.As a conclusion, we isolated and further molecularly characterized non-basal cells exhibiting neuroendocrine and progenitor functions from TRAMP tumors, thus creating preclinical models for NE-PC in vivo and in vitro. Our findings may help in developing novel treatment approaches as well as biomarkers within this entity.
Presenting Author: Maximilian Marhold, Department for Internal Medicine I, Oncology, Medical University of Vienna, Währinger Gürtel, 1090 Vienna, Austria. Email: firstname.lastname@example.org