Biomedical Engineering Reference
In-Depth Information
Fig. 1 Immuno-fluorescent
staining of a primary human
colon carcinoma shows a
small population of
CD133
+
epithelial cells
This glycosylated membrane protein is associated with immature cell types in a
variety of tissues including brain and the hematopoietic system (Bhatia, 2001).
Moreover, in a variety of brain tumors CD133 enriches for tumor-initiating
cells (Singh et al., 2004). Low numbers of CD133-expressing cells have also
recently been found in normal colon tissue (O'Brien et al., 2007). The function
of the CD133 protein remains elusive to this point but is believed to be involved
in plasma membrane physiology since its expression is highly restricted to
membrane protrusions and co-localizes with membrane cholesterol (Mizrak
et al., 2008). Severe retinal degeneration occurs in individuals homozygous for a
frameshift mutation in the CD133 gene, suggesting a role for CD133 in photo-
receptor disk morphogenesis (Maw et al., 2000).
In 2007 it was shown by three separate groups that as few as 100-3000
CD133
+
cells were able to initiate a new tumor while up to 10
10
5
-6
10
6
CD133
cells failed to grow a tumor upon subcutaneous injection (Ricci-Vitiani
et al., 2007; Todaro et al., 2007a) or injection in the renal capsule (O'Brien et al.,
2007). This indeed suggests that selecting the CD133
+
cell fraction results in
enrichment for cells with tumor-initiating capacities, i.e., the cancer stem cells.
Besides CD133, other markers have been implicated in describing the colon-
cancer stem cell-containing population (Table 2). For example the CD44
+
/
ESA
high
cells have also been reported to contain the cancer stem cell population
(Dalerba et al., 2007). CD44 is an adhesion molecule and a Wnt target gene that
is known to be expressed in the lower parts of the crypts in normal colon.
There are some indications that the putative normal colon precursor cell marker
Musashi-1 is also present in colon-cancer stem cells (Todaro et al., 2007b).
