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

Marta Santisteban, Jennifer M. Reiman, Michael K. Asiedu, Marshall D. Behrens, Aziza Nassar, Kimberly R. Kalli, Paul Haluska, James N. Ingle, Lynn C. Hartmann, Masoud H. Manjili, Derek C. Radisky, Soldano Ferrone, Keith L. Knutson

Research output: Contribution to journalArticlepeer-review

320 Scopus citations


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 -/10CD44 +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.

Original languageEnglish (US)
Pages (from-to)2887-2895
Number of pages9
JournalCancer research
Issue number7
StatePublished - Apr 1 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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