Biomedical Engineering Reference
In-Depth Information
1982). Elevated expression of ABC transporters is associated with an increased
resistance to chemotoxic agents compared to non-side-population (SP) cells
(Goodell et al., 1996; Gutova et al., 2007). SP cells isolated by the efflux of
Hoeschst 33342 by ABC transporters with stem cell characteristics have been
characterized in NSCLC and in clinical specimens of lung cancer cell lines.
Further evidence supporting that CSCs have features of immortality and quies-
cence is demonstrated by the fact that certain SP cells contain high levels of
telomerase mRNA and decreased levels of MCM7, a proliferation marker
(Wicha et al., 2006; Ho et al., 2007). Purified SP cells were cultured in vitro and
showed a greater invasion potential. They produced not only more SP subpopu-
lations but also non-SP subsets, repopulating the original presorted cell line.
Furthermore in vivo inoculation of these SP cells into mice proved that smaller
number of cells (inoculums) were required to generate malignant xenografts in
non-obese diabetic-severe combined immunodeficiency mice, suggesting that
these cell populations had increased tumorigenicity compared to non-SP cells
(Ho et al., 2007).
We will now explore the most important cell surface markers in pulmonary
stem cells and highlight their contribution to the advancement of our knowl-
edge in this field.
Cell Surface Markers
The robust identification and targeting of human pulmonary CSCs will lead to
novel modalities for lung cancer diagnosis and treatment. Enormous financial
efforts are being made toward finding those small cellular populations respon-
sible for resistance to traditional cytotoxic therapies. The identification of stout
CSCs markers that are expressed extracellularly and independent of functional
stem cell assays is therefore important to dissect the functional mechanisms
leading to the transformation of normal stem cells into CSCs (Lowry and
Richter, 2007).
CD117 (c-Kit)
Expression of CD117 and its ligand, a stem cell factor in pulmonary neuroen-
docrine tumors, was identified in the 1990s (Hibi et al., 1991). CD117 is related
to poor prognosis in early stage lung adenocarcinoma and squamous cancer
patients, even though in advanced disease its expression is only found in about a
third of patients (Pelosi et al., 2004). Interestingly, phase II clinical trials failed
to demonstrate the clinical efficacy of the Abl/c-Kit/PDGF inhibitor (Imatinib)
in lung cancer, and no mutations of CD117 were found in these tumors, in
contrast to GI stromal tumors (GIST). This inefficacy was also true for lung
cancer patients selected for expression of c-Kit, suggesting that CD117 is
unlikely to mark an early progenitor in lung cancer (Altundag et al., 2005; Dy
et al., 2005; Gross et al., 2006).
