Biomedical Engineering Reference
In-Depth Information
must have three characteristics: the ability to self-renew to allowmaintenance of
a population of undifferentiated stem cell pool throughout life; a strict regula-
tion of stem cell numbers; and the capacity to differentiate in order to clonally
repopulate functional cells within a tissue (Al-Hajj et al., 2004). Stem cells differ
in their intrinsic ability to self-renew and differentiate (Bixby et al., 2002). The
concept of 'cancer stem cell' describes a cancer cell that has the power to self-
renew resulting in another cancerous stem cell as well as a cell that will give rise
to the phenotypically diverse cancer cell populations (Wicha et al., 2006; Sell,
2004; Houghton et al., 2007) (Figs. 2 and 3). These latter cells are thought to
represent the bulk-tumor proliferative cell pool that responds to chemora-
diotherapy, leaving the cancer stem cell population unaffected. Eventually
this results in tumor repopulation and disease recurrence (Houghton et al.,
2007). Cancer stem cells were initially discovered in hematological cancers.
After transplantation, only a small subpopulation of these cells was able to
extensively proliferate and repopulate (Park et al., 1971; Bruce and Van Der
Gaag, 1963; Wodinsky and Kensler, 1966; Bergsagel and Valeriote, 1968). In the
cancer stem cell model, the disruption of genes responsible for the regulation of
self-renewal is predictably important. There is considerable evidence demonstrat-
ing that only a subset of cells in a particular cancer displays characteristics of self-
renewal. It is proposed that the microenvironment or the niche, as explained
T
RACHEA
B
RONCHI
NEB
B
RONCHIOLES
BADJ
A
LVEOLI
Fig. 3 Stem cell niches in the tracheobronchopulmonary tree
Diagram of the human airway and some of the lung niches along its proximal-to-distal
tracheopulmonary distribution. These distinct microenvironments are thought to harvest a
diverse group of pulmonary stem cells that may be responsible for the heterogeneous types of
lung carcinomas. Squamous cell carcinomas arise in the upper airways in a transitional
manner from the submucosal glands. Neuroendocrine cells are likely to be responsible for
small cell carcinomas. Stem cells localizing distally in the airway may be the culprits for
bronchoalveolar carcinomas as well as adenocarcinomas of the lung. NEB neuroepithelial
body, BADJ bronchioalveolar duct junction
