Biomedical Engineering Reference
In-Depth Information
Breast Cancer Stem Cells
Bert Gold and Michael Dean
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 spe-
cifically distinguish tumor-initiating cells from their progeny. Herein we
present a review of the embryogenesis of the human breast, with an empha-
sis on the endocrine and epithelial-mesenchyme interactions required for
proper development of tissues in the niche. We expand our conceptualiza-
tion to include the relationship to the seed and soil hypothesis, and immu-
noediting 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 thera-
peutic interventions.
Contents
1
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
168
2 Breast Anatomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
169
3 Breast Embryology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
170
The content of this publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government.
M. Dean (*)
Human Genetics Section, Laboratory of Experimental Immunology, Cancer
Inflammation Program, Center for Cancer Research, NCI-Frederick, Frederick,
MD 21703, USA