PMID- 19938015
OWN - NLM
STAT- MEDLINE
DCOM- 20100325
LR  - 20211020
IS  - 1097-0045 (Electronic)
IS  - 0270-4137 (Print)
IS  - 0270-4137 (Linking)
VI  - 70
IP  - 5
DP  - 2010 Apr 1
TI  - Human prostate sphere-forming cells represent a subset of basal epithelial cells 
      capable of glandular regeneration in vivo.
PG  - 491-501
LID - 10.1002/pros.21083 [doi]
AB  - BACKGROUND: Prostate stem/progenitor cells function in glandular development and 
      maintenance. They may be targets for tumor initiation, so characterization of 
      these cells may have therapeutic implications. Cells from dissociated tissues 
      that form spheres in vitro often represent stem/progenitor cells. A subset of 
      human prostate cells that form prostaspheres were evaluated for self-renewal and 
      tissue regeneration capability in the present study. METHODS: Prostaspheres were 
      generated from 59 prostatectomy specimens. Lineage marker expression and 
      TMPRSS-ERG status was determined via immunohistochemistry and fluorescence in 
      situ hybridization (FISH). Subpopulations of prostate epithelial cells were 
      isolated by cell sorting and interrogated for sphere-forming activity. Tissue 
      regeneration potential was assessed by combining sphere-forming cells with rat 
      urogenital sinus mesenchyme (rUGSM) subcutaneously in immunocompromised mice. 
      RESULTS: Prostate tissue specimens were heterogeneous, containing both benign and 
      malignant (Gleason 3-5) glands. TMPRSS-ERG fusion was found in approximately 70% 
      of cancers examined. Prostaspheres developed from single cells at a variable rate 
      (0.5-4%) and could be serially passaged. A basal phenotype 
      (CD44+CD49f+CK5+p63+CK8-AR-PSA-) was observed among sphere-forming cells. 
      Subpopulations of prostate cells expressing tumor-associated calcium signal 
      transducer 2 (Trop2), CD44, and CD49f preferentially formed spheres. In vivo 
      implantation of sphere-forming cells and rUGSM regenerated tubular structures 
      containing discreet basal and luminal layers. The TMPRSS-ERG fusion was absent in 
      prostaspheres derived from fusion-positive tumor tissue, suggesting a 
      survival/growth advantage of benign prostate epithelial cells. CONCLUSION: Human 
      prostate sphere-forming cells self-renew, have tissue regeneration capability, 
      and represent a subpopulation of basal cells.
CI  - (c) 2009 Wiley-Liss, Inc.
FAU - Garraway, Isla P
AU  - Garraway IP
AD  - Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, 
      California, USA. igarraway@mednet.ucla.edu
FAU - Sun, Wenyi
AU  - Sun W
FAU - Tran, Chau P
AU  - Tran CP
FAU - Perner, Sven
AU  - Perner S
FAU - Zhang, Bao
AU  - Zhang B
FAU - Goldstein, Andrew S
AU  - Goldstein AS
FAU - Hahm, Scott A
AU  - Hahm SA
FAU - Haider, Maahum
AU  - Haider M
FAU - Head, Christian S
AU  - Head CS
FAU - Reiter, Robert E
AU  - Reiter RE
FAU - Rubin, Mark A
AU  - Rubin MA
FAU - Witte, Owen N
AU  - Witte ON
LA  - eng
GR  - CA-16042/CA/NCI NIH HHS/United States
GR  - F31 HG000117-05/HG/NHGRI NIH HHS/United States
GR  - AI-28697/AI/NIAID NIH HHS/United States
GR  - F31 HG000117/HG/NHGRI NIH HHS/United States
GR  - P30 CA016042/CA/NCI NIH HHS/United States
GR  - P30 AI028697/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Prostate
JT  - The Prostate
JID - 8101368
RN  - 0 (AC133 Antigen)
RN  - 0 (Antigens, CD)
RN  - 0 (CD44 protein, human)
RN  - 0 (Glycoproteins)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (Integrin alpha6)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Peptides)
RN  - 0 (TMPRSS2-ERG fusion protein, human)
SB  - IM
MH  - AC133 Antigen
MH  - Adult
MH  - Aged
MH  - Antigens, CD/analysis
MH  - Cell Lineage
MH  - Epithelial Cells/*physiology
MH  - Gene Rearrangement
MH  - Glycoproteins/analysis
MH  - Humans
MH  - Hyaluronan Receptors/analysis
MH  - Immunohistochemistry
MH  - Integrin alpha6/analysis
MH  - Male
MH  - Middle Aged
MH  - Oncogene Proteins, Fusion/analysis/genetics
MH  - Peptides/analysis
MH  - Prostate/*cytology
MH  - Prostatic Neoplasms/pathology
MH  - Regeneration
MH  - Stem Cells/*physiology
PMC - PMC2885946
MID - NIHMS187861
EDAT- 2009/11/26 06:00
MHDA- 2010/03/26 06:00
CRDT- 2009/11/26 06:00
PHST- 2009/11/26 06:00 [entrez]
PHST- 2009/11/26 06:00 [pubmed]
PHST- 2010/03/26 06:00 [medline]
AID - 10.1002/pros.21083 [doi]
PST - ppublish
SO  - Prostate. 2010 Apr 1;70(5):491-501. doi: 10.1002/pros.21083.