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PMID: 20405247 Published · ppublish English Journal Article

The CD44+/CD24- phenotype relates to 'triple-negative' state and unfavorable prognosis in breast cancer patients.

Medical oncology (Northwood, London, England) ·Vol. 28 ·No. 3 ·2011-09-00 ·Pages 745-52

Giatromanolaki A, Sivridis E, Fiska A, Koukourakis MI

Abstract

Breast carcinomas have been reported to contain a subpopulation of CD44+/CD24- tumor cells with stem cell-like properties. This study investigates the significance of these two molecules in connection with tumor aggression and prognosis. The phenotypic profile of 139 breast carcinomas was investigated in paraffin sections using markers previously associated with stem cell-like properties (CD44, CD24), the "triple-state" (ER, PR, c-erb-B2), and angiogenesis (CD31). Tumors with >10% of CD44 and CD24 cancer cells were considered positive. The prevalence of CD44+ and CD24+ breast carcinomas in the series was 51.8% and 41.7%, respectively. Patients with the CD44(+)/CD24(-) phenotype had a 10-year lower median age at presentation and harbored tumors with a triple-negative state. They experienced an unfavorable prognosis. Lack of CD44 expression was associated with lymph node involvement, regardless of CD24 status, whereas the lack of both CD44 and CD24 was connected with high histologic grade and unfavorable prognosis which, notably, was the worse among all phenotypes. In multivariate analysis, the CD44(-)/CD24(-) phenotype, the nodal involvement, the vascular density and the ER-/PR-/c-erbB-2-profile were independent prognostic variables. It is concluded that assessment of the CD44/CD24 status may reveal distinct subgroups of breast cancer patients with different clinical behavior. The unsatisfactory response of the triple-negative tumors to current chemotherapy and their intimate link with the CD44(+)/CD24(-) phenotype, makes CD44 targeting an attractive therapeutic alternative for breast cancer patients. The strong association between the CD44(-)/CD24(-) phenotype and prognosis requires further investigation.

MeSH Terms
Adult Aged Aged, 80 and over Biomarkers, Tumor/genetics,metabolism Breast Neoplasms/genetics,metabolism,pathology CD24 Antigen/biosynthesis Female Humans Hyaluronan Receptors/biosynthesis Immunohistochemistry Kaplan-Meier Estimate Middle Aged Phenotype Prognosis Receptor, ErbB-2/biosynthesis,genetics Receptors, Estrogen/biosynthesis,genetics Receptors, Progesterone/biosynthesis,genetics
Chemicals
Biomarkers, Tumor CD24 Antigen CD24 protein, human CD44 protein, human Hyaluronan Receptors Receptors, Estrogen Receptors, Progesterone Receptor, ErbB-2
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Giatromanolaki Alexandra
Department of Pathology, Democritus University of Thrace Medical School, and University General Hospital of Alexandroupolis, P.O. Box 12, 68100, Alexandroupolis, Greece. agiatrom@med.duth.gr
Sivridis Efthimios
Fiska Aliki
Koukourakis Michael I
References (48)
48 references, click to expand
  1. [Pilot study on the correlation between high incidence of CD44+/CD24 -/low/ABCG2- cells and poor prognosis in breast cancer].
    Beijing Da Xue Xue Bao Yi Xue Ban. 2008 Oct 18;40(5):465-70 PMID: 18931706
  2. Stem cells in mammary development and carcinogenesis: implications for prevention and treatment.
    Stem Cell Rev. 2005;1(3):207-13 PMID: 17142857
  3. c-erbB-2 and the "triple-state" in early breast carcinomas.
    Med Oncol. 2010 Sep;27(3):578-84 PMID: 19548127
  4. Mammosphere culture of metastatic breast cancer cells enriches for tumorigenic breast cancer cells.
    Breast Cancer Res. 2008;10(3):R52 PMID: 18541018
  5. CD24 affects CXCR4 function in pre-B lymphocytes and breast carcinoma cells.
    J Cell Sci. 2006 Jan 15;119(Pt 2):314-25 PMID: 16390867
  6. CD24 expression causes the acquisition of multiple cellular properties associated with tumor growth and metastasis.
    Cancer Res. 2005 Dec 1;65(23):10783-93 PMID: 16322224
  7. CD44 is overexpressed in basal-like breast cancers but is not a driver of 11p13 amplification.
    Breast Cancer Res Treat. 2010 Feb;120(1):95-109 PMID: 19350388
  8. CD24 expression has a prognostic impact in breast carcinoma.
    Pathol Res Pract. 2009;205(8):524-33 PMID: 19243896
  9. c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer.
    N Engl J Med. 1994 May 5;330(18):1260-6 PMID: 7908410
  10. The CD44+/CD24- phenotype is enriched in basal-like breast tumors.
    Breast Cancer Res. 2008;10(3):R53 PMID: 18559090
  11. Role of CD44s and CD44v6 on human breast cancer cell adhesion, migration, and invasion.
    Exp Mol Pathol. 2009 Apr;86(2):95-100 PMID: 19167378
  12. The epithelial-mesenchymal transition generates cells with properties of stem cells.
    Cell. 2008 May 16;133(4):704-15 PMID: 18485877
  13. The role of the CD44 transmembrane and cytoplasmic domains in co-ordinating adhesive and signalling events.
    J Cell Sci. 2004 Jan 26;117(Pt 3):373-80 PMID: 14702383
  14. CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis.
    Breast Cancer Res. 2006;8(5):R59 PMID: 17062128
  15. The response of CD24(-/low)/CD44+ breast cancer-initiating cells to radiation.
    J Natl Cancer Inst. 2006 Dec 20;98(24):1777-85 PMID: 17179479
  16. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy.
    J Natl Cancer Inst. 2008 May 7;100(9):672-9 PMID: 18445819
  17. CD24, a mucin-type glycoprotein, is a ligand for P-selectin on human tumor cells.
    Blood. 1997 May 1;89(9):3385-95 PMID: 9129046
  18. Isolation of CD24(high) and CD24(low/-) cells from MCF-7: CD24 expression is positively related with proliferation, adhesion and invasion in MCF-7.
    Cancer Lett. 2007 Dec 8;258(1):98-108 PMID: 17950993
  19. Prospective identification of tumorigenic breast cancer cells.
    Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3983-8 PMID: 12629218
  20. CD24 overexpression in cancer development and progression: a meta-analysis.
    Oncol Rep. 2009 Nov;22(5):1149-56 PMID: 19787233
  21. Hyaluronan-CD44 interaction activates stem cell marker Nanog, Stat-3-mediated MDR1 gene expression, and ankyrin-regulated multidrug efflux in breast and ovarian tumor cells.
    J Biol Chem. 2008 Jun 20;283(25):17635-51 PMID: 18441325
  22. The angiogenic "vascular endothelial growth factor/flk-1(KDR) receptor" pathway in patients with endometrial carcinoma: prognostic and therapeutic implications.
    Cancer. 2001 Nov 15;92(10):2569-77 PMID: 11745191
  23. Tissue-specific promoters active in CD44+CD24-/low breast cancer cells.
    Cancer Res. 2008 Jul 15;68(14):5533-9 PMID: 18632604
  24. CD44 is of functional importance for colorectal cancer stem cells.
    Clin Cancer Res. 2008 Nov 1;14(21):6751-60 PMID: 18980968
  25. Lymphatic metastasis of breast cancer cells is associated with differential gene expression profiles that predict cancer stem cell-like properties and the ability to survive, establish and grow in a foreign environment.
    Int J Oncol. 2009 Aug;35(2):297-308 PMID: 19578743
  26. Characterisation of breast cancer cell lines and establishment of a novel isogenic subclone to study migration, invasion and tumourigenicity.
    Clin Exp Metastasis. 2008;25(5):549-57 PMID: 18386134
  27. Possible treatment strategies for triple-negative breast cancer on the basis of molecular characteristics.
    Breast Cancer. 2009;16(4):275-80 PMID: 19408071
  28. Estrogen-mediated downregulation of CD24 in breast cancer cells.
    Int J Cancer. 2008 Jul 1;123(1):66-72 PMID: 18404683
  29. Suppression of human colon cancer tumors in nude mice by siRNA CD44 gene therapy.
    Exp Mol Pathol. 2007 Dec;83(3):332-40 PMID: 17945212
  30. Dynamic regulation of CD24 and the invasive, CD44posCD24neg phenotype in breast cancer cell lines.
    Breast Cancer Res. 2009;11(6):R82 PMID: 19906290
  31. CD44 attenuates metastatic invasion during breast cancer progression.
    Cancer Res. 2005 Aug 1;65(15):6755-63 PMID: 16061657
  32. Phenotypic and functional characterization of human mammary stem/progenitor cells in long term culture.
    PLoS One. 2009;4(4):e5329 PMID: 19390630
  33. CD24 promotes invasion of glioma cells in vivo.
    J Neuropathol Exp Neurol. 1999 Aug;58(8):795-802 PMID: 10446804
  34. Tumor-endothelial interaction links the CD44(+)/CD24(-) phenotype with poor prognosis in early-stage breast cancer.
    Neoplasia. 2009 Oct;11(10):987-1002 PMID: 19794958
  35. Brca1 breast tumors contain distinct CD44+/CD24- and CD133+ cells with cancer stem cell characteristics.
    Breast Cancer Res. 2008;10(1):R10 PMID: 18241344
  36. Targeting CD24 for treatment of colorectal and pancreatic cancer by monoclonal antibodies or small interfering RNA.
    Cancer Res. 2008 Apr 15;68(8):2803-12 PMID: 18413748
  37. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties.
    Cancer Res. 2005 Jul 1;65(13):5506-11 PMID: 15994920
  38. CD44 expression is associated with increased survival in node-negative invasive breast carcinoma.
    Clin Cancer Res. 2005 May 1;11(9):3309-14 PMID: 15867228
  39. CD24 and human carcinoma: tumor biological aspects.
    Biomed Pharmacother. 2005 Oct;59 Suppl 2:S351-4 PMID: 16507407
  40. Anticancer therapeutics: targeting macromolecules and nanocarriers to hyaluronan or CD44, a hyaluronan receptor.
    Mol Pharm. 2008 Jul-Aug;5(4):474-86 PMID: 18547053
  41. The clinicopathologic and prognostic significance of CD44+/CD24(-/low) and CD44-/CD24+ tumor cells in invasive breast carcinomas.
    Hum Pathol. 2008 Jul;39(7):1096-102 PMID: 18495204
  42. CD44-mediated oncogenic signaling and cytoskeleton activation during mammary tumor progression.
    J Mammary Gland Biol Neoplasia. 2001 Jul;6(3):287-97 PMID: 11547898
  43. CD24 induces localization of beta1 integrin to lipid raft domains.
    Biochem Biophys Res Commun. 2008 Jan 4;365(1):35-41 PMID: 17980703
  44. Growth-inhibitory and tumor- suppressive functions of p53 depend on its repression of CD44 expression.
    Cell. 2008 Jul 11;134(1):62-73 PMID: 18614011
  45. Signal transduction in lymphocytic and myeloid cells via CD24, a new member of phosphoinositol-anchored membrane molecules.
    J Immunol. 1990 Jan 15;144(2):638-41 PMID: 2153173
  46. Prevalence of CD44+/CD24-/low cells in breast cancer may not be associated with clinical outcome but may favor distant metastasis.
    Clin Cancer Res. 2005 Feb 1;11(3):1154-9 PMID: 15709183
  47. Mapping of CD24 and homologous sequences to multiple chromosomal loci.
    Genomics. 1994 Jul 1;22(1):154-61 PMID: 7959762
  48. Cortactin underpins CD44-promoted invasion and adhesion of breast cancer cells to bone marrow endothelial cells.
    Oncogene. 2006 Oct 5;25(45):6079-91 PMID: 16652145
Article Info
Journal
Medical oncology (Northwood, London, England)
Abbr.
Med Oncol
ISSN
1559-131X
DOI
10.1007/s12032-010-9530-3
Email
agiatrom@med.duth.gr
Published
2011-09-00
Epub
2010-00-20
Pages
745-52
Language
English
Region
United States
NLM ID
9435512
Subset
IM
External Links
PubMed source DOI: 10.1007/s12032-010-9530-3 View journal details
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