Biomedical Engineering Reference
In-Depth Information
As a follow-up these investigators sought to characterize c-myc oncogene
amplification in the resulting HMEC tumors (Ben-Porath et al., 2008). Because
this gene frequently mutated in breast cancer, amplification is taken to signify
initiation of a process of additional events that recapitulate further genetic
alterations typically found in the spontaneous development of breast cancer
in patients.
9 Activation of Stem Cells and Cancer
Most stem cells in the body remain in a dormant state. These cells are sur-
rounded by other, differentiated cells within the tissue microenvironment often
described as a ''niche''. The cells of the niche regulate the stem cells via cell-cell
contacts, interactions with the extracellular matrix, and secretion of inhibitory
factors. The disruption of the niche microenvironment, through infection,
inflammation, tissue damage, or chemical assault, can activate the division of
the stem cells (see Fig. 1). The activated stem cell gives rise to additional stem
cells as well as cells committed to differentiate. These new cells repair the
damaged area of tissue, and the stem cells return to their quiescent state.
Virtually all of the agents described to confer a risk for cancer also result in
tissue alteration (and therefore activation of stem cells) including radiation,
wounding, chemical damage, infectious agents, and inflammation.
Normal Stem Cell
in niche
Tissue Damage
Repair
Chronic
Tissue
Damage
Tumor Progression
Mutations
Activated Stem Cells
Tumor
Fig. 1 Activation of stem cells and tumor progression. Stem cells are quiescent in the niche.
Upon tissue damage they divide and repair the damage. However, chronic tissue damage leads
to continually divided (activated) stem cells that are the target for later mutagenic events that
create a cancer stem cell and a tumor
Cancer can be thought of as a disease resulting from the abnormal growth of
stem cells, resulting from chronic activation of stem cells (caused by disruption
of the niche) and leading to the long-term proliferation of the stem cells.
Chronically dividing stem cells are a target for additional mutagenic agents
