Home LiteratureArticle Details
PMID: 15886885 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

The mammary gland "side population": a putative stem/progenitor cell marker?

Journal of mammary gland biology and neoplasia ·Vol. 10 ·No. 1 ·2005-01-00 ·Pages 37-47

Smalley MJ, Clarke RB

Abstract

Hematopoietic Stem Cells have been isolated by their ability to pump out Hoechst 33342 dye and form a distinct population definable by flow cytometry--the Side Population (SP). The membrane pump Bcrp has been identified as the molecular determinant of the SP phenotype. An SP population with Bcrp activity has been defined in a number of tissues, including mouse mammary and human breast epithelium, and it has been proposed that the SP phenotype is a universal stem cell marker. Studies of mouse and human breast SP suggest that the population is undifferentiated but capable of differentiating into epithelial structures of both luminal and myoepithelial lineages both in vitro and in vivo. However, evidence that the SP is enriched for stem cells is, at the moment, only correlative, and there are potentially confounding technical issues. We still await formal proof that the SP contains a stem cell population.

MeSH Terms
ATP-Binding Cassette Transporters/genetics,metabolism Animals Biomarkers/analysis Breast Neoplasms/metabolism,pathology Humans Mammary Glands, Animal/cytology,metabolism Mammary Glands, Human/cytology,metabolism Stem Cells/cytology,metabolism
Chemicals
ATP-Binding Cassette Transporters Biomarkers
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Smalley Matthew J
The Breakthrough Breast Cancer Centre, The Institute of Cancer Research, London, United Kingdom.
Clarke Robert B
References (63)
63 references, click to expand
  1. Molecular phenotype of airway side population cells.
    Am J Physiol Lung Cell Mol Physiol. 2004 Apr;286(4):L624-30 PMID: 12909587
  2. Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species.
    Nat Med. 1997 Dec;3(12 ):1337-45 PMID: 9396603
  3. Hoechst 33342-induced apoptosis is associated with decreased immunoreactive topoisomerase I and topoisomerase I-DNA complex formation.
    Ann Clin Lab Sci. 2001 Apr;31(2):187-98 PMID: 11337909
  4. Functional and molecular characterisation of mammary side population cells.
    Breast Cancer Res. 2003;5(1):R1-8 PMID: 12559051
  5. A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia.
    Blood. 2001 Aug 15;98 (4):1166-73 PMID: 11493466
  6. Side population cells in human and mouse epidermis lack stem cell characteristics.
    Exp Cell Res. 2004 Apr 15;295(1):79-90 PMID: 15051492
  7. Sca-1(pos) cells in the mouse mammary gland represent an enriched progenitor cell population.
    Dev Biol. 2002 May 1;245(1):42-56 PMID: 11969254
  8. Cells of the hepatic side population contribute to liver regeneration and can be replenished with bone marrow stem cells.
    Haematologica. 2003 Apr;88(4):368-78 PMID: 12681963
  9. An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions.
    J Natl Cancer Inst. 1975 Aug;55(2):231-73 PMID: 169369
  10. Reconstruction of functionally normal and malignant human breast tissues in mice.
    Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4966-71 PMID: 15051869
  11. Atypical multidrug resistance: breast cancer resistance protein messenger RNA expression in mitoxantrone-selected cell lines.
    J Natl Cancer Inst. 1999 Mar 3;91(5):429-33 PMID: 10070941
  12. Hepatic oval cells have the side population phenotype defined by expression of ATP-binding cassette transporter ABCG2/BCRP1.
    Am J Pathol. 2003 Jul;163(1):3-9 PMID: 12819005
  13. Hoechst dye efflux reveals a novel CD7(+)CD34(-) lymphoid progenitor in human umbilical cord blood.
    Blood. 2000 Sep 15;96(6):2125-33 PMID: 10979957
  14. Regulation of human breast epithelial stem cells.
    Cell Prolif. 2003 Oct;36 Suppl 1:45-58 PMID: 14521515
  15. Tissue reconstitution models of breast cancer.
    Cancer Surv. 1993;16:79-96 PMID: 8348540
  16. Novel method for the isolation and characterisation of the putative prostatic stem cell.
    Cytometry A. 2003 Aug;54(2):89-99 PMID: 12879455
  17. Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell.
    Dev Biol. 1996 Apr 10;175(1):1-13 PMID: 8608856
  18. Persistent expression of the ATP-binding cassette transporter, Abcg2, identifies cardiac SP cells in the developing and adult heart.
    Dev Biol. 2004 Jan 1;265(1):262-75 PMID: 14697368
  19. Flow cytometric analysis of neural stem cells in the developing and adult mouse brain.
    J Neurosci Res. 2002 Sep 15;69(6):837-47 PMID: 12205677
  20. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells.
    J Clin Invest. 2001 Jun;107(11):1395-402 PMID: 11390421
  21. Human limbal epithelium contains side population cells expressing the ATP-binding cassette transporter ABCG2.
    FEBS Lett. 2004 May 7;565(1-3):6-10 PMID: 15135043
  22. Growth and differentiation of progenitor/stem cells derived from the human mammary gland.
    Exp Cell Res. 2004 Jul 15;297(2):444-60 PMID: 15212947
  23. Characterization of neurosphere cell phenotypes by flow cytometry.
    Cytometry. 2000 Jul 1;40(3):245-50 PMID: 10878568
  24. Identification of a novel estrogen response element in the breast cancer resistance protein (ABCG2) gene.
    Cancer Res. 2004 Feb 15;64(4):1247-51 PMID: 14973083
  25. Experimental mammary epithelial morphogenesis in an in vivo model: evidence for distinct cellular progenitors of the ductal and lobular phenotype.
    Breast Cancer Res Treat. 1996;39(1):21-31 PMID: 8738603
  26. A multidrug resistance transporter from human MCF-7 breast cancer cells.
    Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15665-70 PMID: 9861027
  27. The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype.
    Nat Med. 2001 Sep;7(9):1028-34 PMID: 11533706
  28. YOPRO-1 permits cytofluorometric analysis of programmed cell death (apoptosis) without interfering with cell viability.
    J Immunol Methods. 1995 Sep 25;185(2):249-58 PMID: 7561136
  29. Spermatogonial stem cells share some, but not all, phenotypic and functional characteristics with other stem cells.
    Proc Natl Acad Sci U S A. 2003 May 27;100(11):6487-92 PMID: 12738887
  30. Cardiac muscle plasticity in adult and embryo by heart-derived progenitor cells.
    Ann N Y Acad Sci. 2004 May;1015:182-9 PMID: 15201159
  31. Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells.
    Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9064-8 PMID: 1384042
  32. A putative human breast stem cell population is enriched for steroid receptor-positive cells.
    Dev Biol. 2005 Jan 15;277(2):443-56 PMID: 15617686
  33. Bcrp1 gene expression is required for normal numbers of side population stem cells in mice, and confers relative protection to mitoxantrone in hematopoietic cells in vivo.
    Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12339-44 PMID: 12218177
  34. The mouse Bcrp1/Mxr/Abcp gene: amplification and overexpression in cell lines selected for resistance to topotecan, mitoxantrone, or doxorubicin.
    Cancer Res. 1999 Sep 1;59(17):4237-41 PMID: 10485464
  35. Fumitremorgin C reverses multidrug resistance in cells transfected with the breast cancer resistance protein.
    Cancer Res. 2000 Jan 1;60(1):47-50 PMID: 10646850
  36. Identification and enrichment of spermatogonial stem cells displaying side-population phenotype in immature mouse testis.
    FASEB J. 2004 Feb;18(2):376-8 PMID: 14688197
  37. Identification of breast cancer resistant protein/mitoxantrone resistance/placenta-specific, ATP-binding cassette transporter as a transporter of NB-506 and J-107088, topoisomerase I inhibitors with an indolocarbazole structure.
    Cancer Res. 2001 Apr 1;61(7):2827-32 PMID: 11306452
  38. Identification of a cancer stem cell in human brain tumors.
    Cancer Res. 2003 Sep 15;63(18):5821-8 PMID: 14522905
  39. De novo testosterone production in luteinizing hormone receptor knockout mice after transplantation of leydig stem cells.
    Endocrinology. 2004 Sep;145(9):4011-5 PMID: 15123536
  40. Development of mouse mammary gland: identification of stages in differentiation of luminal and myoepithelial cells using monoclonal antibodies and polyvalent antiserum against keratin.
    J Histochem Cytochem. 1986 Aug;34(8):1037-46 PMID: 2426332
  41. Stem cells and breast cancer: A field in transit.
    Nat Rev Cancer. 2003 Nov;3(11):832-44 PMID: 14668814
  42. Folate deprivation results in the loss of breast cancer resistance protein (BCRP/ABCG2) expression. A role for BCRP in cellular folate homeostasis.
    J Biol Chem. 2004 Jun 11;279(24):25527-34 PMID: 15047700
  43. Direct identification and enrichment of retinal stem cells/progenitors by Hoechst dye efflux assay.
    Invest Ophthalmol Vis Sci. 2003 Jun;44(6):2764-73 PMID: 12766085
  44. Dissociation between steroid receptor expression and cell proliferation in the human breast.
    Cancer Res. 1997 Nov 15;57(22):4987-91 PMID: 9371488
  45. The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria.
    Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15649-54 PMID: 12429862
  46. Distinct populations of forebrain neural stem and progenitor cells can be isolated using side-population analysis.
    J Neurosci. 2003 Nov 19;23 (33):10703-9 PMID: 14627655
  47. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo.
    J Exp Med. 1996 Apr 1;183(4):1797-806 PMID: 8666936
  48. Hematopoietic and nonhematopoietic potentials of Hoechst(low)/side population cells isolated from adult rat kidney.
    Kidney Int. 2004 May;65(5):1604-14 PMID: 15086898
  49. Stem cells, cancer, and cancer stem cells.
    Nature. 2001 Nov 1;414(6859):105-11 PMID: 11689955
  50. Hoechst 33342-induced apoptosis is associated with intracellular accumulation of E2F-1 protein in BC3H-1 myocytes and HL-60 cells.
    Arch Pathol Lab Med. 2001 Jan;125(1):99-104 PMID: 11151061
  51. The stem cell marker Bcrp/ABCG2 enhances hypoxic cell survival through interactions with heme.
    J Biol Chem. 2004 Jun 4;279(23 ):24218-25 PMID: 15044468
  52. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell.
    Nat Med. 1997 Jul;3(7):730-7 PMID: 9212098
  53. In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells.
    Genes Dev. 2003 May 15;17 (10 ):1253-70 PMID: 12756227
  54. Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line.
    Proc Natl Acad Sci U S A. 2004 Jan 20;101(3):781-6 PMID: 14711994
  55. Side population keratinocytes resembling bone marrow side population stem cells are distinct from label-retaining keratinocyte stem cells.
    J Invest Dermatol. 2003 Nov;121(5):1095-103 PMID: 14708612
  56. Prospective identification of tumorigenic breast cancer cells.
    Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8 PMID: 12629218
  57. The transforming activity of Wnt effectors correlates with their ability to induce the accumulation of mammary progenitor cells.
    Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4158-63 PMID: 15020770
  58. Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction.
    Blood. 2004 Dec 1;104(12):3581-7 PMID: 15297308
  59. Side population cells and Bcrp1 expression in lung.
    Am J Physiol Lung Cell Mol Physiol. 2003 Jul;285(1):L97-104 PMID: 12626330
  60. Akt signaling regulates side population cell phenotype via Bcrp1 translocation.
    J Biol Chem. 2003 Oct 3;278(40):39068-75 PMID: 12851395
  61. Nestin-positive progenitor cells derived from adult human pancreatic islets of Langerhans contain side population (SP) cells defined by expression of the ABCG2 (BCRP1) ATP-binding cassette transporter.
    Biochem Biophys Res Commun. 2002 May 3;293(2):670-4 PMID: 12054520
  62. Cancer stem cells persist in many cancer cell lines.
    Cell Cycle. 2004 Apr;3(4):414-5 PMID: 15004528
  63. A distinct "side population" of cells with high drug efflux capacity in human tumor cells.
    Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14228-33 PMID: 15381773
Article Info
Journal
Journal of mammary gland biology and neoplasia
Abbr.
J Mammary Gland Biol Neoplasia
ISSN
1083-3021
Published
2005-01-00
Pages
37-47
Language
English
Region
United States
NLM ID
9601804
Subset
IM
Grants
Breast Cancer Now · 2004NOV42 · United Kingdom
Breast Cancer Now · BREAST CANCER NOW RESEARCH CENTRE · United Kingdom
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com