title: Identification of Different Classes of Luminal Progenitor Cells within Prostate Tumors.
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.
authors.affiliation: Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Supreet
authors.initials: S
authors.lastname: Agarwal
authors.affiliation: Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Hynes
authors.affiliation: Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Heather S
authors.initials: HS
authors.lastname: Tillman
authors.affiliation: Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Ross
authors.initials: R
authors.lastname: Lake
authors.affiliation: Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Wassim G
authors.initials: WG
authors.lastname: Abou-Kheir
authors.affiliation: Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.affiliation: Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Orla M
authors.initials: OM
authors.lastname: Casey
authors.affiliation: Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Amir H
authors.initials: AH
authors.lastname: Ameri
authors.affiliation: Center for Advanced Preclinical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Philip L
authors.initials: PL
authors.lastname: Martin
authors.affiliation: Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
authors.forename: Juan Juan
authors.initials: JJ
authors.lastname: Yin
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Iaquinta
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Wouter R
authors.initials: WR
authors.lastname: Karthaus
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, 3584CT Utrecht, the Netherlands.
authors.forename: Hans C
authors.initials: HC
authors.lastname: Clevers
authors.affiliation: 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.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Sawyers
authors.affiliation: Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA. Electronic address: kellyka@mail.nih.gov.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Kelly
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D019070:Cell Lineage; D002469:Cell Separation; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000473:pathology; D005434:Flow Cytometry; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000473:pathology*; D009940:Organoids; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000473:pathology*
keywords: castration; heterogeneity; luminal; prostate cancer; stem/progenitor cells