title: The PSA(-/lo) prostate cancer cell population harbors self-renewing long-term tumor-propagating cells that resist castration.
abstract: Prostate cancer (PCa) is heterogeneous and contains both differentiated and undifferentiated tumor cells, but the relative functional contribution of these two cell populations remains unclear. Here we report distinct molecular, cellular, and tumor-propagating properties of PCa cells that express high (PSA(+)) and low (PSA(-/lo)) levels of the differentiation marker PSA. PSA(-/lo) PCa cells are quiescent and refractory to stresses including androgen deprivation, exhibit high clonogenic potential, and possess long-term tumor-propagating capacity. They preferentially express stem cell genes and can undergo asymmetric cell division to generate PSA(+) cells. Importantly, PSA(-/lo) PCa cells can initiate robust tumor development and resist androgen ablation in castrated hosts, and they harbor highly tumorigenic castration-resistant PCa cells that can be prospectively enriched using ALDH(+)CD44(+)α2β1(+) phenotype. In contrast, PSA(+) PCa cells possess more limited tumor-propagating capacity, undergo symmetric division, and are sensitive to castration. Altogether, our study suggests that PSA(-/lo) cells may represent a critical source of castration-resistant PCa cells.
authors.affiliation: Department of Molecular Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Science Park, Smithville, TX 78957, USA.
authors.forename: Jichao
authors.initials: J
authors.lastname: Qin
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Brian
authors.initials: B
authors.lastname: Laffin
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Grace
authors.initials: G
authors.lastname: Choy
authors.forename: Collene R
authors.initials: CR
authors.lastname: Jeter
authors.forename: Tammy
authors.initials: T
authors.lastname: Calhoun-Davis
authors.forename: Hangwen
authors.initials: H
authors.lastname: Li
authors.forename: Ganesh S
authors.initials: GS
authors.lastname: Palapattu
authors.forename: Shen
authors.initials: S
authors.lastname: Pang
authors.forename: Kevin
authors.initials: K
authors.lastname: Lin
authors.forename: Jiaoti
authors.initials: J
authors.lastname: Huang
authors.forename: Ivan
authors.initials: I
authors.lastname: Ivanov
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Mahipal V
authors.initials: MV
authors.lastname: Suraneni
authors.forename: Dean G
authors.initials: DG
authors.lastname: Tang
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000473:pathology* / Q000601:surgery; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D060049:Asymmetric Cell Division; D002369:Castration; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000473:pathology* / Q000601:surgery
chemical_list: D000943:Antigens, Differentiation; D017430:Prostate-Specific Antigen