Biomedical Engineering Reference
In-Depth Information
Table 2 Colon-cancer stem cell markers
Markers
Function
Percentage(%)
Publication
CD133
+
Unknown
0.2-20
O'Brien et al. (2007),
Ricci-Vitiani et al.
(2007), Todaro
et al. (2007a)
CD44
+
/ESA
high*
/
CD166
+
CD44; adhesion molecule,
ESA; adhesion
molecule, CD166
(ALCAM); adhesion
molecule
0.2-58 (mean
11.8%)
Dalerba et al. (2007)
ESA epithelial-specific antigen
However, direct isolation of cells expressing this marker is not feasible at this
point since this protein resides intracellularly. The frequency of tumor-initiat-
ing cells, even in the CD133-enriched population, is very low. The real cancer
stem cell number is estimated to be, on average, 1 in every 262 CD133
+
cells
(O'Brien et al., 2007). Moreover, clear overlap exists between the CD133
+
and CD44
+
/ESA
high
populations, indicating that a combination of these
markers may further enrich for the colon-cancer stem cell population. This
could indicate a hierarchy in stem cells and progenitor cells, as seen in the
CD34
+
leukemia-initiating cell population in acute myeloid leukemia. Thus,
additional markers are needed to purify the colon-cancer stem cell population
further and to describe a possible progenitor phase.
4.3 In Vivo Differentiation
The tumors that arise after injection of the colon-cancer stem cell-containing
cell population in mice are a phenocopy of the original malignancy. This means
that the typical adenocarcinoma-like morphology is preserved and largely the
same markers are expressed. To achieve this it is necessary that the injected
cancer stem cells give rise to the more differentiated cells present in a CRC and,
indeed, some cells within the xenografts do show expression of differentiation
markers such as cytokeratin-20 (CK-20), CDX2, Muc-2, and Villin. These
proteins are also present in the differentiated cells in normal colon crypts.
Moreover, there is clear evidence for the production of mucin in these xeno-
grafts. This suggests that functional differentiation of colon-cancer stem cells
also occurs. In addition, tumor cells are observed that express CD133, indicat-
ing that a colon-cancer stem cell population is preserved. These tumors are also
able to propagate the tumor in a second round of transplantation and are still
able to give rise to colon-cancer stem cell cultures (see later). In this way the two
defining criteria for colon-cancer stem cells, self-renewal and generation of
more differentiated cells, have been met.
