Biomedical Engineering Reference
In-Depth Information
Although for hematological, breast, and brain cancers many putative CSC
markers have been readily identified, this, unfortunately, is not the case so far in
potential human BASCs. The two cell surface markers used to identify mouse
BASCs have proven to be inadequate in humans: Sca-1 does not have a human
homolog, and CD34 staining does not correlate to the putative SP stem cells
described in NSCLC (Ho et al., 2007). These results highlight the importance of
further work to confirm whether a single, normal lung stem progenitor is
sufficient to define the CSC populations in each subtype of lung cancer or
whether it indicates multiple origins responsible for the cellularity of the
cancers.
4 Conclusions
The growing field of pulmonary stem cells is resulting in useful study
models that can be used to gain newer perspectives in the way cancer is
investigated. These perspectives are certainly not devoid of controversy
due to the many missing jigsaw pieces in the field. The discovery of stout
cell surface markers will hopefully lead to the identification of putative
human lung homeostatic and cancer stem cells as it has been done in other
types of human cancer (Table 3). We have explored the role of the most
important developmental pathways in the organogenesis of the bronchopul-
monary tree to then highlight how these very same pathways can crosstalk
through poorly understood mechanisms, to orchestrate the maintenance of
the respiratory tree and its potential self-renewing stem cell populations dur-
ing adulthood. Because of the large number of genes in these signaling trans-
duction pathways and their specific functions in differing physiological and
pathological contexts, a considerable proportion of developmental fates dur-
ing the life of an animal are controlled by the action of these signals on stem
cells and their specific niches or microenvironments. We have increasing
evidence that the adequate function of stem cells is dependent on their niches,
and these in turn are complex microenvironments composed of the extracel-
lular matrix and various other cellular and non-cellular components that are
also influenced by the paracrine actions of the developmental pathways
described herewith (Table 3). All this taken together, it has been suggested
that cancer is the result of a permanent state of injury repair, where the
accumulation of oncogenic events may 'lock' activated previously homeo-
static stem cells in a permanent abnormally driven mode that results in the
transformation of these 'normal' stem cells into CSCs (Beachy et al., 2004)
(Fig. 2). Understanding the complexity of these processes will hopefully
allow scientists and clinicians to translating knowledge about the signaling
machinery into novel pharmacologically relevant therapies for human lung
cancers.
