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Cell, Tumor, and Stem Cell Biology |
Departments of 1Oncology, 2Immunology, and 3Anatomic Pathology, Mayo Clinic, Rochester, Minnesota; 4Department of Oncology, Clinica Universidad de Navarra, Pamplona, Spain; 5Department of Microbiology and Immunology, VCU School of Medicine, Massey Cancer Center, Richmond, Virginia; 6Department of Biochemistry and Molecular Biology, Mayo Clinic, Jacksonville, Florida; and 7Departments of Surgery, Immunology and Pathology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania
* To whom correspondence should be addressed. E-mail: knutson.keith{at}mayo.edu.
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Abstract |
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The breast cancer stem cell (BCSC) hypotheses suggest that breast cancer is derived from a single tumor-initiating cell with stem-like properties, but the source of these cells is unclear. We previously observed that induction of an immune response against an epithelial breast cancer led in vivo to the T-cell–dependent outgrowth of a tumor, the cells of which had undergone epithelial to mesenchymal transition (EMT). The resulting mesenchymal tumor cells had a CD24-/loCD44+ phenotype, consistent with BCSCs. In the present study, we found that EMT was induced by CD8 T cells and the resulting tumors had characteristics of BCSCs, including potent tumorigenicity, ability to reestablish an epithelial tumor, and enhanced resistance to drugs and radiation. In contrast to the hierarchal cancer stem cell hypothesis, which suggests that breast cancer arises from the transformation of a resident tissue stem cell, our results show that EMT can produce the BCSC phenotype. These findings have several important implications related to disease progression and relapse. [Cancer Res 2009;69(7):OF1–9]
Key Words: EMT, breast cancer stem cells, generation in vivo, chemoresistance, radioresistance
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  F. Reim, Y. Dombrowski, C. Ritter, M. Buttmann, S. Hausler, M. Ossadnik, M. Krockenberger, D. Beier, C. P. Beier, J. Dietl, et al. Immunoselection of Breast and Ovarian Cancer Cells with Trastuzumab and Natural Killer Cells: Selective Escape of CD44high/CD24low/HER2low Breast Cancer Stem Cells Cancer Res., October 15, 2009; 69(20): 8058 - 8066. [Abstract] [Full Text] [PDF]
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