Stem Cells and Lung Cancer - Stem Cells and Cancer - page 211

CD44
CD44 is a ubiquitously expressed multispan transmembrane cell surface
adhesion glycoprotein. It has functions in cell-matrix and cell-cell interac-
tions and it has been linked to poor prognosis and resistance to chemother-
apy in many cancers (Liu and Jiang, 2006). CD44 can be found in collagen,
fibronectin, fibrinogen, hyaluronic acid, FGF2, laminin, and other
heparin-binding growth factors (Liu and Jiang, 2006; Naor et al., 2002).
CD44 and its association to metastatic progression suggests its protagon-
ism in the survival of disseminated cells, and this is enhanced through its
upregulation by osteopontin (Desai et al., 2007). CD44 is increased in both
SCLC and NSCLC and it correlates with survival (Le et al., 2006; Lee
et al., 2005).
CD133 (Prominin-1)
Prominin-1 is a glycoprotein with five membrane-spanning domains initially
identified in endothelial cells (Shmelkov et al., 2005). It is also found in brain,
colonic, and pancreatic cancer-initiating stem cells (Vescovi et al., 2006). This
protein, like CD44, has been linked to drug resistance and interestingly brain-
tumor-derived CD133 þ -sorted cell lines exhibit a unique gene expression
profile (Beier et al., 2007). A recent study in humans from a histologically
heterogeneous group of lung cancers analyzed SCLC and NSCLC tumors and
identified a CD133 þ subset of cells, which was able to produce lung tumor
spheres with the ability to differentiate and produce tumors in vivo. This
population of cells was found to be very similar to a rare subpopulation of
CD133 þ cells present in normal mouse lung, which undergoes significant
expansion following airway injury after naphthalene treatment (Eramo
et al., 2008). Expression of the ABC transporter responsible for the SP
phenotype together with the embryonic stem cell markers, OCT4 and
NANOG, was linked to chemoresistance in the CD133 þ spheres (Eramo
et al., 2008).
Miscellaneous Markers
In human SCLC cell lines, a small population of urokinase-type plasminogen
activator (uPAR)-positive CD87 cells was identified. A subset of these cells
showed increased clonogenic activity in vitro (Gutova et al., 2007). The pre-
sence of both uPAR þ and uPAR cells in the resultant colonies suggests a
multilineage potential of those stem cell populations. However, when uPAR
cells were isolated from the SCLC cell lines they lacked clonogenic activity.
uPAR plays a role in cell adhesion and migration. Consequently, the fact that
high levels of uPAR have been linked to various human cancers is not surprising
(Romer et al., 2004).