Abstract LB-276: The identification and characterization of prostate adenocarcinoma tumor initiating cells

Abstract

Abstract Primary prostate cancer is typically of luminal phenotype. However, little is known about the stem/progenitor properties of transformed luminal tumor cells as they fail to survive in culture. Using the organoid culture methodology, we show two distinct luminal progenitors in aggressive Pten/Tp53-null mouse model of prostate cancer. Not only did tumors contain previously described multipotent progenitors, but also a major population of committed luminal progenitors. The distinction between committed luminal and multipotent organoids was also evident in subcutaneous grafts as tumors of adenocarcinoma or multilineage histological phenotypes were observed, respectively. Moreover, using organoids we show that the self-renewing capacity of luminal-committed progenitors is a tumor-specific property, absent in benign luminal cells. Further, a significant fraction of luminal progenitors displayed resistance to in vivo castration as well as to androgen receptor inhibition ex vivo. Importantly, 3D organoid techniques have allowed us to relate our findings in humans as we can successfully grow similar luminal tumor populations from patient derived xenografts (PDXs) models of prostate cancer. In all, these data reveal two distinct luminal tumorigenic populations in mouse models of prostate cancer, providing insight into luminal tumor initiating cells in prostate cancer that can also influence response to therapy. Citation Format: Supreet Agarwal, Paul Hynes, Ross Lake, Lei Fang, Heather Tillman, Mike Beshiri, Keith Jansson, Wouter Karthaus, Philip Iaquinta, Charles Sawyers, Kathleen Kelly. The identification and characterization of prostate adenocarcinoma tumor initiating cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-276.