MOLECULAR CHARACTERIZATION OF CANCER STEM CELLS FROM PROSTATE CANCER XENOGRAFTS

You have accessJournal of UrologyStem Cell Research: Stem Cell Research II1 Apr 2018MP81-16 MOLECULAR CHARACTERIZATION OF CANCER STEM CELLS FROM PROSTATE CANCER XENOGRAFTS Sofia Karkampouna, Maria De Menna, Markus Germann, Joel Grosjean, Peter Clark Gray, George N. Thalmann, and Marianna Kruithof-de Julio Sofia KarkampounaSofia Karkampouna More articles by this author , Maria De MennaMaria De Menna More articles by this author , Markus GermannMarkus Germann More articles by this author , Joel GrosjeanJoel Grosjean More articles by this author , Peter Clark GrayPeter Clark Gray More articles by this author , George N. ThalmannGeorge N. Thalmann More articles by this author , and Marianna Kruithof-de JulioMarianna Kruithof-de Julio More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2724AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer recurrence after androgen deprivation therapy is attributed to the existence of androgen-independent cancer stem cells, which differentiate into androgen-dependent cancer cells that reinitiate tumor growth. Phenotypic properties of cancer stem cell subpopulations versus highly proliferative progenitor cells remain to be further characterized in terms of androgen receptor signaling, quiescence/proliferation, tumorigenicity and therapy-resistance. METHODS To address the molecular basis of CSC switch from Androgen-dependency to independency we employed two patient-derived xenograft models (LAPC-9, BM-18) that have different androgen sensitivity properties. We performed microarray and proteomic analysis of tumor tissues prior to/ following castration and after androgen replacement. Subpopulations are isolated based on combination of selected markers to assess their transcriptomic changes, in vitro and in vivo self-renewal. RESULTS Castration induces rapid tumor volume decrease of BM-18 and stabilization of tumor burden in the LAPC-9, reflecting different androgen dependent cell states. Proteomic analysis of bulk BM-18 tumors (intact, 14 days post castration, 50 days post Androgen replacement), indicates an enrichment of stem cell markers upon castration; CD44, NKX3.1 and ALDH1 isoforms. Microarray analysis has confirmed upregulation of CD44 and ALDH1A1 at castrated state, versus downregulation upon androgen replacement at early time points (24 hours). We isolated CD44+/-ALDHhigh/low subpopulations by flow cytometry for transcriptome analysis. Castration in the BM-18 model induces an increase in the subpopulations of CD44+/ALDHlow (from 0.44% to 2.3%) and CD44+/ALDHhigh (from 0.06% to 0.38%). However, the same subpopulations are not increased in the LAPC-9 model upon castration, while only the CD44-/ALDHhigh subset is enriched (from 3.5% to 7.1%). Organoids derived from bulk BM-18 and LAPC-9 tumors are reestablishing tumor formation upon intraosseous inoculation. CONCLUSIONS Different androgen-independent cancer stem cell subpopulations may be distinguished by the ALDH activity status in combination with CD44. The androgen-independent cells in the BM-18 androgen-dependent model are reflected by enrichment of CD44 expression, as well as a rare double positive population. In the androgen-independent LAPC-9 model, CD44 expression is decreased potentially reflecting androgen-dependent CD44+ cells, and ALDH activity increased in CD44- cells. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1102-e1103 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Sofia Karkampouna More articles by this author Maria De Menna More articles by this author Markus Germann More articles by this author Joel Grosjean More articles by this author Peter Clark Gray More articles by this author George N. Thalmann More articles by this author Marianna Kruithof-de Julio More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...