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Int J Biol Sci 2008; 4(3):133-142. doi:10.7150/ijbs.4.133

Research Paper

Identification and characterization of cancer initiating cells from BRCA1 related mammary tumors using markers for normal mammary stem cells

Athanassios Vassilopoulos1, Rui-Hong Wang1, Constantinos Petrovas2, David Ambrozak2, Richard Koup2, Chu-Xia Deng1

1. Genetics of Development and Disease Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, MD 20892, USA.
2. Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, Maryland, MD 20892, USA.

Abstract

It is hypothesized that cancer stem cells arise either from normal stem cells or from progenitor cells that have gained the ability to self-renew. Here we determine whether mammary cancer stem cells can be isolated by using antibodies that have been used for the isolation of normal mammary stem cells. We show that BRCA1 mutant cancer cell lines contained a subpopulation of CD24+CD29+ or CD24+CD49f+ cells that exhibited increased proliferation and colony forming ability in vitro, and enhanced tumor-forming ability in vivo. The purified CD24+CD29+ cells could differentiate and reconstitute the heterogeneity found in parental cells when plated as a monolayer. Under low-attachment conditions, we detected “tumorspheres” only in the presence of double positive cells, which maintained their ability to self-renew. Furthermore, CD24+CD29+ cells could form tubular structures reminiscent of the mammary ductal tree when grown in three-dimensional cultures, implying that these cancer cells maintain some of the characteristics of the normal stem cells. Nevertheless, they could still drive tumor formation since as low as 500 double positive cells immediately after sorting from BRCA1 mutant primary tumors were able to form tumors with the same heterogeneity found in the original tumors. These data provide evidence that breast cancer stem cells originate from normal stem cells and advance our understanding of BRCA1-associated tumorigenesis with possible implications for future cancer treatment.

Keywords: breast cancer, BRCA1, stem cells, CD24, CD29

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How to cite this article:
Vassilopoulos A, Wang RH, Petrovas C, Ambrozak D, Koup R, Deng CX. Identification and characterization of cancer initiating cells from BRCA1 related mammary tumors using markers for normal mammary stem cells. Int J Biol Sci 2008; 4(3):133-142. doi:10.7150/ijbs.4.133. Available from http://www.ijbs.com/v04p0133.htm