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Publication : Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells.

First Author  Santisteban M Year  2009
Journal  Cancer Res Volume  69
Issue  7 Pages  2887-95
PubMed ID  19276366 Mgi Jnum  J:147366
Mgi Id  MGI:3840393 Doi  10.1158/0008-5472.CAN-08-3343
Citation  Santisteban M, et al. (2009) Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells. Cancer Res 69(7):2887-95
abstractText  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(-/lo)CD44(+) 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.
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