Biomedical Engineering Reference
In-Depth Information
(presented above for leukemia) that cancer stem cells are resistant to standard
therapies. Now we will address the exciting recent observations that suggest the
potential for that cancer stem cells to be isolated by the use of stem cell markers,
allowing investigators to study the properties of these isolated cancer stem cells.
2.2 Isolation of Cancer Stem Cells?
The recent interest in cancer stem cells derives from the possibility that cancer
stem cells can be isolated by flow cytometry using stem cell markers, for
example, breast (Al-Hajj et al., 2003; Shipitsin et al., 2007) and liver cancer
(Yin et al., 2007; Ma et al., 2007, 2008; Fang et al., 2008; Yan et al., 2008; Zen
et al., 2007; Yamashita et al., 2008; Kaposi-Novak et al., 2006) markers .
2.2.1 Breast Cancer
Human primary breast cancer cells can be fractionated by cell sorting into two
major populations: CD44+CD24
ESA+ and CD44
CD24+ESA
. ESA
stands for epithelial cell-specific antigen. Primary tumors show mixtures of
these two cells types (Shipitsin et al., 2007) and there is a high degree of
heterogeneity of expression of these markers by immunohistochemistry, indi-
cating that tumors are composed of at least two types of cells (Liao et al., 2007).
One of six transplantation takes was obtained by injection of 100 cells from a
very highly purified CD44+CD24
ESA+ population (Al-Hajj et al., 2003).
Thus, the frequency of tumor-initiating cells in the purified population was
similar to that reported in 1952 for whole tumor cell populations by Reinhard
et al. (1952b); this group obtained 6% takes with injection of 18 cells. A higher
transplantation frequency could be obtained when CD24
CD44+ESA+
low
cells were sorted from CD24
CD44+ESA+
high
cells, but the number of trans-
plant attempts was too low for significance to be attained (Al-Hajj et al., 2003).
In any case, these results suggest that two types of breast cancer cells can be
separated on the basis of these markers: a stem cell-like population and a
transit-amplifying type cell population. After transplantation of the
CD44+CD24
ESA+ stem cell-like breast cancer cells, the growing tumor
reconstitutes both cell populations, suggesting that the tumor-initiating stem
cell-like population could produce progeny expression markers of the non-
tumor-initiating transit-amplifying like cell population (Al-Hajj et al., 2003).
On the other hand, the properties of the non-stem population were not
reported. Shipitsin et al. (2007) found that the CD44+ cells were more stem-
like than were the CD24+ cells, in terms of molecular phenotype; they pro-
posed that the CD24+ cells may ''evolve'' from the CD44+ population. This
hypothesis presumes, of course, that both fractions are part of the epithelial
cancer cell population. In our laboratory, when breast cancers from transgenic
mouse models were examined, similar fractionations of breast cancer cells based
