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

Publication ,  Journal Article
Liu, X; Chen, X; Rycaj, K; Chao, H-P; Deng, Q; Jeter, C; Liu, C; Honorio, S; Li, H; Davis, T; Suraneni, M; Laffin, B; Qin, J; Li, Q ...
Published in: Oncotarget
September 15, 2015

Human cancers are heterogeneous containing stem-like cancer cells operationally defined as cancer stem cells (CSCs) that possess great tumor-initiating and long-term tumor-propagating properties. In this study, we systematically dissect the phenotypic, functional and tumorigenic heterogeneity in human prostate cancer (PCa) using xenograft models and >70 patient tumor samples. In the first part, we further investigate the PSA-/lo PCa cell population, which we have recently shown to harbor self-renewing long-term tumor-propagating cells and present several novel findings. We show that discordant AR and PSA expression in both untreated and castration-resistant PCa (CRPC) results in AR+PSA+, AR+PSA-, AR-PSA-, and AR-PSA+ subtypes of PCa cells that manifest differential sensitivities to therapeutics. We further demonstrate that castration leads to a great enrichment of PSA-/lo PCa cells in both xenograft tumors and CRPC samples and systemic androgen levels dynamically regulate the relative abundance of PSA+ versus PSA-/lo PCa cells that impacts the kinetics of tumor growth. We also present evidence that the PSA-/lo PCa cells possess distinct epigenetic profiles. As the PSA-/lo PCa cell population is heterogeneous, in the second part, we employ two PSA- (Du145 and PC3) and two PSA+ (LAPC9 and LAPC4) PCa models as well as patient tumor cells to further dissect the clonogenic and tumorigenic subsets. We report that different PCa models possess distinct tumorigenic subpopulations that both commonly and uniquely express important signaling pathways that could represent therapeutic targets. Our results have important implications in understanding PCa cell heterogeneity, response to clinical therapeutics, and cellular mechanisms underlying CRPC.

Duke Scholars

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Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

September 15, 2015

Volume

6

Issue

27

Start / End Page

23959 / 23986

Location

United States

Related Subject Headings

  • Signal Transduction
  • Receptors, Androgen
  • RNA, Messenger
  • Prostatic Neoplasms
  • Prostate-Specific Antigen
  • Promoter Regions, Genetic
  • Phenotype
  • Neoplastic Stem Cells
  • Neoplasm Transplantation
  • Mice
 

Citation

APA
Chicago
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Liu, X., Chen, X., Rycaj, K., Chao, H.-P., Deng, Q., Jeter, C., … Tang, D. G. (2015). Systematic dissection of phenotypic, functional, and tumorigenic heterogeneity of human prostate cancer cells. Oncotarget, 6(27), 23959–23986. https://doi.org/10.18632/oncotarget.4260
Liu, Xin, Xin Chen, Kiera Rycaj, Hsueh-Ping Chao, Qu Deng, Collene Jeter, Can Liu, et al. “Systematic dissection of phenotypic, functional, and tumorigenic heterogeneity of human prostate cancer cells.Oncotarget 6, no. 27 (September 15, 2015): 23959–86. https://doi.org/10.18632/oncotarget.4260.
Liu X, Chen X, Rycaj K, Chao H-P, Deng Q, Jeter C, et al. Systematic dissection of phenotypic, functional, and tumorigenic heterogeneity of human prostate cancer cells. Oncotarget. 2015 Sep 15;6(27):23959–86.
Liu, Xin, et al. “Systematic dissection of phenotypic, functional, and tumorigenic heterogeneity of human prostate cancer cells.Oncotarget, vol. 6, no. 27, Sept. 2015, pp. 23959–86. Pubmed, doi:10.18632/oncotarget.4260.
Liu X, Chen X, Rycaj K, Chao H-P, Deng Q, Jeter C, Liu C, Honorio S, Li H, Davis T, Suraneni M, Laffin B, Qin J, Li Q, Yang T, Whitney P, Shen J, Huang J, Tang DG. Systematic dissection of phenotypic, functional, and tumorigenic heterogeneity of human prostate cancer cells. Oncotarget. 2015 Sep 15;6(27):23959–23986.

Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

September 15, 2015

Volume

6

Issue

27

Start / End Page

23959 / 23986

Location

United States

Related Subject Headings

  • Signal Transduction
  • Receptors, Androgen
  • RNA, Messenger
  • Prostatic Neoplasms
  • Prostate-Specific Antigen
  • Promoter Regions, Genetic
  • Phenotype
  • Neoplastic Stem Cells
  • Neoplasm Transplantation
  • Mice