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Cell Rep. 2015 Dec 15;13(10):2147-58. doi: 10.1016/j.celrep.2015.10.077. Epub 2015 Nov 25.

Identification of Different Classes of Luminal Progenitor Cells within Prostate Tumors.

Author information

1
Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
2
Center for Advanced Preclinical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
3
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
4
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, 3584CT Utrecht, the Netherlands.
5
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
6
Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA. Electronic address: kellyka@mail.nih.gov.

Abstract

Primary prostate cancer almost always has a luminal phenotype. However, little is known about the stem/progenitor properties of transformed cells within tumors. Using the aggressive Pten/Tp53-null mouse model of prostate cancer, we show that two classes of luminal progenitors exist within a tumor. Not only did tumors contain previously described multipotent progenitors, but also a major population of committed luminal progenitors. Luminal cells, sorted directly from tumors or grown as organoids, initiated tumors of adenocarcinoma or multilineage histological phenotypes, which is consistent with luminal and multipotent differentiation potentials, respectively. Moreover, using organoids we show that the ability of luminal-committed progenitors to self-renew is a tumor-specific property, absent in benign luminal cells. Finally, a significant fraction of luminal progenitors survived in vivo castration. In all, these data reveal two luminal tumor populations with different stem/progenitor cell capacities, providing insight into prostate cancer cells that initiate tumors and can influence treatment response.

KEYWORDS:

castration; heterogeneity; luminal; prostate cancer; stem/progenitor cells

PMID:
26628377
PMCID:
PMC4840850
DOI:
10.1016/j.celrep.2015.10.077
[Indexed for MEDLINE]
Free PMC Article

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