Breast cancer stem cells

Abstract

One aspect of the analogy between embryogenesis and cancer is the emphasis on rapid cell division and self-renewal from a small number of immortal cells. A key understanding in developmental biology is the concept of determination and its consequences, in the form of lineage totipotency, pluripotency, multipotency, and unipotency. The normal cell fate decision point involves epigenetic mechanisms that are dysregulated in neoplasia. These dysregulated cell proliferation triggers are posited to specifically distinguish tumor-initiating cells from their progeny. Herein we present a review of the embryogenesis of the human breast, with an emphasis on the endocrine and epithelial-mesenchyme interactions required for proper development of tissues in the niche. We expand our conceptualization to include the relationship to the seed and soil hypothesis, and immunoediting theory. We expand on the new paradigm by explaining the relevance of side populations, plating efficiency, and tumor-initiating cells to cancer stem cell theory. Finally, we provide some suggestions for signal transduction pathway interventions, viz., that of the hedgehog/patched pathway, that might make breast cancer more amenable to specific therapeutic interventions. © Springer Science+Business Media, LLC 2009. All rights reserved.