Enriched CD44(+)/CD24(-) population drives the aggressive phenotypes presented in triple-negative breast cancer (TNBC).

The mechanism underlying the aggressive behaviors of triple negative breast cancer (TNBC) is not well characterized yet. The association between cancer stem cell (CSC) population and the aggressive behaviors of TNBC has not been established. We found the CD44(+)/CD24(-) cell population was enriched in TNBC tissues and cell lines, with a higher capacity of proliferation, migration, invasion and tumorigenicity as well as lower adhesion ability. The CD44(+)/CD24(-) cell population with cancer stem cell-like properties may play an important role in the aggressive behaviors of TNBC. This discovery may lead to new therapeutic strategies targeting CD44(+)/CD24(-) cell population in TNBC.

[1]  W. Woodward,et al.  Primary breast cancer patients with high risk clinicopathologic features have high percentages of bone marrow epithelial cells with ALDH activity and CD44⁺CD24lo cancer stem cell phenotype. , 2011, European Journal of Cancer.

[2]  L. Miele,et al.  Cancer stem cells – an old idea that’s new again: implications for the diagnosis and treatment of breast cancer , 2007, Expert opinion on biological therapy.

[3]  R. Huang,et al.  Epithelial-Mesenchymal Transitions in Development and Disease , 2009, Cell.

[4]  I. Giannopoulou,et al.  The clinicopathologic and prognostic significance of CD44+/CD24(-/low) and CD44-/CD24+ tumor cells in invasive breast carcinomas. , 2008, Human pathology.

[5]  L. Carey,et al.  Triple-negative breast cancer: disease entity or title of convenience? , 2010, Nature Reviews Clinical Oncology.

[6]  Xue-qing Xu,et al.  Association between Polymorphisms in the Promoter Regions of Matrix Metalloproteinases (MMPs) and Risk of Cancer Metastasis: A Meta-Analysis , 2012, PloS one.

[7]  Carlos Caldas,et al.  Molecular heterogeneity of breast carcinomas and the cancer stem cell hypothesis , 2007, Nature Reviews Cancer.

[8]  Anthony Rhodes,et al.  American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. , 2007, Archives of pathology & laboratory medicine.

[9]  C. Wells,et al.  Predictive markers in breast cancer – the present , 2007, Histopathology.

[10]  R. Tibshirani,et al.  Repeated observation of breast tumor subtypes in independent gene expression data sets , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Maria Athelogou,et al.  Prevalence of CD44+/CD24-/low cells in breast cancer may not be associated with clinical outcome but may favor distant metastasis. , 2005, Clinical cancer research : an official journal of the American Association for Cancer Research.

[12]  M. Schuelke,et al.  Comparative analysis of uncoupling protein 4 distribution in various tissues under physiological conditions and during development. , 2009, Biochimica et biophysica acta.

[13]  A. Gown,et al.  Immunohistochemical and Clinical Characterization of the Basal-Like Subtype of Invasive Breast Carcinoma , 2004, Clinical Cancer Research.

[14]  B. Zhou,et al.  New insights of epithelial-mesenchymal transition in cancer metastasis. , 2008, Acta biochimica et biophysica Sinica.

[15]  R. Wells,et al.  First among equals: The cancer cell hierarchy , 2006, Leukemia & lymphoma.

[16]  André F. Vieira,et al.  Breast cancer stem cell markers CD44, CD24 and ALDH1: expression distribution within intrinsic molecular subtype , 2011, Journal of Clinical Pathology.

[17]  H. Clevers Wnt/beta-catenin signaling in development and disease. , 2006, Cell.

[18]  D. Schols,et al.  CXCL12-CXCR4 axis in angiogenesis, metastasis and stem cell mobilization. , 2010, Current pharmaceutical design.

[19]  R. Beroukhim,et al.  Molecular definition of breast tumor heterogeneity. , 2007, Cancer cell.

[20]  A. Minn,et al.  Triple negative breast cancer initiating cell subsets differ in functional and molecular characteristics and in γ-secretase inhibitor drug responses , 2013, EMBO molecular medicine.

[21]  Q. Chu,et al.  Chemokine receptor CXCR4 overexpression predicts recurrence for hormone receptor-positive, node-negative breast cancer patients. , 2011, Surgery.

[22]  P. Fumoleau,et al.  The Paradox of Triple Negative Breast Cancer: Novel Approaches to Treatment , 2012, The breast journal.

[23]  S. Morrison,et al.  Prospective identification of tumorigenic breast cancer cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[24]  A. Giatromanolaki,et al.  The CD44+/CD24− phenotype relates to ‘triple-negative’ state and unfavorable prognosis in breast cancer patients , 2011, Medical oncology.

[25]  George Stoica,et al.  Expression of MMP2, MMP9 and MMP3 in Breast Cancer Brain Metastasis in a Rat Model , 2005, Clinical & Experimental Metastasis.

[26]  I. Stamenkovic,et al.  Identification of hyaluronic acid binding sites in the extracellular domain of CD44 , 1993, Journal of Cell Biology.

[27]  Nicholas J. Wang,et al.  Characterization of a naturally occurring breast cancer subset enriched in epithelial-to-mesenchymal transition and stem cell characteristics. , 2009, Cancer research.

[28]  M. Dowsett,et al.  American society of clinical oncology/college of american pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. , 2010, Journal of oncology practice.

[29]  Jason I. Herschkowitz,et al.  Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer , 2010, Breast Cancer Research.

[30]  Raghu Kalluri,et al.  The basics of epithelial-mesenchymal transition. , 2009, The Journal of clinical investigation.

[31]  Anthony Rhodes,et al.  American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. , 2006, Archives of pathology & laboratory medicine.

[32]  M. Hung,et al.  The Expression Patterns of ER, PR, HER2, CK5/6, EGFR, Ki-67 and AR by Immunohistochemical Analysis in Breast Cancer Cell Lines , 2010, Breast cancer : basic and clinical research.

[33]  Wen-Lin Kuo,et al.  A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. , 2006, Cancer cell.

[34]  Kornelia Polyak,et al.  Breast Tumor Heterogeneity: Cancer Stem Cells or Clonal Evolution? , 2007, Cell cycle.

[35]  Xinquan Lü,et al.  CD44+/CD24− Cells Are Transit Progenitors and Do Not Determine the Molecular Subtypes and Clinical Parameters in Breast Carcinomas , 2011, Ultrastructural pathology.

[36]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[37]  I. Ellis,et al.  Expression profiling technology: its contribution to our understanding of breast cancer , 2007, Histopathology.

[38]  P. Pelicci,et al.  Biological and Molecular Heterogeneity of Breast Cancers Correlates with Their Cancer Stem Cell Content , 2010, Cell.

[39]  L. Bourguignon,et al.  CD44 Interaction with Tiam1 Promotes Rac1 Signaling and Hyaluronic Acid-mediated Breast Tumor Cell Migration* , 2000, The Journal of Biological Chemistry.

[40]  M. Manjili,et al.  CD44(+)/CD24(-/low) cancer stem/progenitor cells are more abundant in triple-negative invasive breast carcinoma phenotype and are associated with poor outcome. , 2012, Human pathology.

[41]  E. Tokunaga,et al.  Topoisomerase IIalpha-positive and BRCA1-negative phenotype: association with favorable response to epirubicin-based regimens for human breast cancers. , 2008, Cancer letters.