title: Human prostate side population cells demonstrate stem cell properties in recombination with urogenital sinus mesenchyme.
abstract: Stem cell enrichment provides a tool to examine prostate stem cells obtained from benign and malignant tissue. Functional assays can enrich stem cells based on common stem cell phenotypes, such as high ATP binding cassette (ABC) transporter mediated efflux of Hoechst substrates (side population assay). This functional assay is based upon mechanisms that protect cells from environmental insult thus contributing to the survival and protection of the stem cell population. We have isolated and analyzed cells digested from twelve clinical prostate specimens based on the side population assay. Prostate stem cell properties of the isolated cells were tested by serial recombination with rat urogenital mesenchyme. Recombinants with side population cells demonstrate an increase in the frequency of human ductal growth and the number of glands per recombinant when compared to recombinants with non-side population cells. Isolated cells were capable of prostatic growth for up to three generations in the recombination assay with as little as 125 sorted prostate cells. The ability to reproducibly use cells isolated by fluorescence activated cell sorting from human prostate tissue is an essential step to a better understanding of human prostate stem cell biology. ABC transporter G2 (ABCG2) was expressed in recombinants from side population cells indicating the side population cells have self-renewal properties. Epithelial cell differentiation of recombinants was determined by immunohistochemical analysis for expression of the basal, luminal, and neuroendocrine markers, p63, androgen receptor, prostate specific antigen, and chromogranin A, respectively. Thus, the ABCG2 expressing side population demonstrates multipotency and self-renewal properties indicating stem cells are within this population.
authors: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors: Barbara A
authors: BA
authors: Foster
authors: Kalyan J
authors: KJ
authors: Gangavarapu
authors: Grinu
authors: G
authors: Mathew
authors: Gissou
authors: G
authors: Azabdaftari
authors: Carl D
authors: CD
authors: Morrison
authors: Austin
authors: A
authors: Miller
authors: Wendy J
authors: WJ
authors: Huss
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002469:Cell Separation; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D008297:Male; D008648:Mesoderm / Q000166:cytology*; D011467:Prostate / Q000166:cytology*; D051381:Rats; D058985:Side-Population Cells / Q000166:cytology*; D014566:Urogenital System / Q000166:cytology*
references: Nat Med. 2001 Sep;7(9):1028-34
references: 11533706
references: J Invest Dermatol. 1986 Jul;87(1):42-6
references: 3522753
references: Stem Cells. 2010 Feb;28(2):344-56
references: 20020426
references: Cancer Res. 2005 Aug 1;65(15):6640-50
references: 16061644
references: J Exp Med. 1996 Apr 1;183(4):1797-806
references: 8666936
references: Proc Natl Acad Sci U S A. 2005 May 10;102(19):6942-7
references: 15860580
references: Cell Cycle. 2009 Apr 1;8(7):1053-61
references: 19270533
references: Acta Anat (Basel). 1992;143(2):139-50
references: 1598820
references: Cytometry A. 2003 Aug;54(2):89-99
references: 12879455
references: Differentiation. 1998 Jul;63(3):131-40
references: 9697307
references: Nature. 2008 Dec 11;456(7223):804-8
references: 18946470
references: PLoS One. 2012;7(4):e34219
references: 22514625
references: PLoS One. 2008 Jul 02;3(7):e2572
references: 18596907
references: Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12339-44
references: 12218177
references: Biol Reprod. 1998 Jul;59(1):93-9
references: 9674998
references: Cancer Cell. 2012 Feb 14;21(2):253-65
references: 22340597
references: Nat Protoc. 2010 Apr;5(4):702-13
references: 20360765
references: Stem Cells Dev. 2009 Dec;18(10):1515-22
references: 19260804
references: Nature. 2008 Dec 4;456(7222):593-8
references: 19052619
references: Differentiation. 2003 Sep;71(7):402-13
references: 12969333
references: Curr Protoc Toxicol. 2011 Feb;Chapter 22:Unit 22.2
references: 21400686
references: Cell Stem Cell. 2011 Feb 4;8(2):136-47
references: 21295271
references: Prostate. 2010 Apr 1;70(5):491-501
references: 19938015
references: Prostate. 2009 Oct 1;69(14):1557-64
references: 19562732
references: Prostate. 2007 Sep 15;67(13):1384-96
references: 17639507
references: Cancer Res. 2001 Nov 15;61(22):8135-42
references: 11719442
references: Stem Cells. 2006 Aug;24(8):1859-68
references: 16644920
references: BMC Urol. 2007 Apr 10;7:6
references: 17425799
references: Stem Cells. 2005 Sep;23(8):1059-65
references: 16002779
references: Cancer Res. 1991 Sep 15;51(18):4924-30
references: 1893381
references: Cancer Res. 1990 Aug 1;50(15):4747-54
references: 2369750
references: J Cell Sci. 2001 Nov;114(Pt 21):3865-72
references: 11719553
references: Prostate. 2009 May 15;69(7):770-3
references: 19204997
references: Stem Cells. 2011 Aug;29(8):1310-4
references: 21674698
references: Cancer Res. 2008 Dec 1;68(23):9703-11
references: 19047148
references: Stem Cells. 2007 Apr;25(4):1029-36
references: 17185610