The PSA(-/lo) prostate cancer cell population harbors self-renewing long-term tumor-propagating cells that resist castration.

Cell Stem Cell
Jichao QinDean G Tang

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.

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Citations

Apr 26, 2014·British Journal of Cancer·J YanD Tang
Apr 12, 2014·Cancers·Jennifer L BishopAmina Zoubeidi
Jan 22, 2014·Cancer Metastasis Reviews·Lei ChangYong Li
Oct 8, 2013·Oncogene·S J VidalJ Domingo-Domenech
Jan 15, 2014·Cancer Metastasis Reviews·Rhonda L BittingAndrew J Armstrong
Sep 5, 2014·Cancer Immunology, Immunotherapy : CII·Roya GhodsAmir-Hassan Zarnani
Jan 26, 2013·The Journal of Clinical Investigation·Max S Wicha
Nov 28, 2013·Proceedings of the National Academy of Sciences of the United States of America·Tanya StoyanovaAndrew S Goldstein
Jun 3, 2014·Cancer Investigation·Nicholas WongDamu Tang
Oct 16, 2015·Prostate Cancer and Prostatic Diseases·A J ArmstrongS J Freedland
Jul 15, 2015·Oncology Letters·Tao Yang, Kiera Rycaj
Feb 6, 2016·Archivum Immunologiae Et Therapiae Experimentalis·Xiukun LinMuhammad Ismail
Oct 7, 2015·Cancer Science·Yoshihiko HirohashiNoriyuki Sato
Feb 18, 2016·Stem Cells International·Alastair H Davies, Amina Zoubeidi
Oct 3, 2012·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Maho Shibata, Michael M Shen
Nov 10, 2012·The Prostate·Edwin E ReyesDonald J Vander Griend
Aug 21, 2014·International Journal of Cancer. Journal International Du Cancer·Ning XieXuesen Dong
Aug 5, 2015·Seminars in Cancer Biology·Qiuhui LiDean G Tang
Aug 25, 2015·Seminars in Cancer Biology·Frédéric R SanterRhiannon V McNeill
Jul 29, 2015·Prostate Cancer and Prostatic Diseases·M J MayerV Venkateswaran
Feb 28, 2016·Biochimica Et Biophysica Acta·John R Packer, Norman J Maitland
May 3, 2015·Endocrine-related Cancer·Jennifer L BishopAmina Zoubeidi
Apr 30, 2015·Medical Oncology·Chunguang YangWilliam Chi Cho
Feb 2, 2013·Cell Cycle·Xin ChenDean G Tang
May 9, 2012·Cell Stem Cell·Max S Wicha

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