Systematic dissection of phenotypic, functional, and tumorigenic heterogeneity of human prostate cancer cells.

摘要: // Xin Liu 1, * , Chen Kiera Rycaj Hsueh-Ping Chao 3 Qu Deng Collene Jeter 1 Can Sofia Honorio Hangwen Li Tammy Davis Mahipal Suraneni Brian Laffin Jichao Qin Qiuhui Tao Yang 2 Pamela Whitney Jianjun Shen Jiaoti Huang 4 Dean G. Tang 2, 3, 5 Department of Epigenetics and Molecular Carcinogenesis, University Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957, USA Stem Cell Institute, Research Center for Translational Medicine, East Hospital, Tongji School Shanghai 200120, China Program in Graduate Biomedical Sciences (GSBS), Houston, 77030, Pathology Laboratory David Geffen UCLA, Los Angeles, CA 90095, Centers Epigenetics, Developmental Biology, RNA Interference Non-Coding RNAs, These authors have contributed equally to this work Correspondence to: Tang, e-mail: dtang@mdanderson.org Keywords: prostate cancer, cancer stem cells, differentiation, heterogeneity Received: April 15, 2015      Accepted: June 12, Published: 24, 2015 ABSTRACT Human cancers are heterogeneous containing stem-like cells operationally defined as (CSCs) that possess great tumor-initiating long-term tumor-propagating properties. In study, we systematically dissect the phenotypic, functional tumorigenic human (PCa) using xenograft models >70 patient tumor samples. first part, further investigate PSA −/lo PCa cell population, which recently shown harbor self-renewing present several novel findings. We show discordant AR expression both untreated castration-resistant (CRPC) results + − subtypes manifest differential sensitivities therapeutics. demonstrate castration leads a enrichment tumors CRPC samples systemic androgen levels dynamically regulate relative abundance versus impacts kinetics growth. also evidence distinct epigenetic profiles. As population is heterogeneous, second employ two (Du145 PC3) (LAPC9 LAPC4) well clonogenic subsets. report different subpopulations commonly uniquely express important signaling pathways could represent therapeutic targets. Our implications understanding heterogeneity, response clinical therapeutics, cellular mechanisms underlying CRPC.