Biomedical Engineering Reference
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proportion of cells ranging from 0.1 to 100% of all cells from transplantable
mouse tumors meet the criteria of a tumor stem cell, i.e., ''regrowth of the
tumour preceded by clonal expansion from a single cell with unlimited prolif-
erative potential.'' He concluded that tumors contain the same populations of
cells as are found in normal tissue, consistent with the proposal of Pierce et al.
for teratocarcinoma (see below; Pierce et al, 1978). On the other hand, Dene-
kamp (1994), considering the same evidence, deduced that the putative cancer
stem cells are merely the least differentiated cells in the cancer population and
appear functionally and kinetically different from the mass of tumor cells. She
concluded that the cancer stem cell is not as clearly definable as the normal
tissue stem cell. The debate has now been renewed (Adams and Strasser, 2008).
For example, Kern and Shibata (2007), using a mathematical analysis, point
out that tumor-initiating capacity could be a varying probabilistic potential for
all tumor cells, rather than a quantal and deterministic feature of a minority of
tumor cells. Identification of tumor-initiating cell populations through the use
of marker phenotypes could preferentially enrich for cells able to transplant
tumors, but even with the best purification systems, the so-called non-tumori-
genic cell population will contain up to 3% of tumorigenic cells (Li et al., 2007).
Because the flow-cytometric separations depend on cell surface markers that
may change expression or be masked by cell surface carbohydrates, it is possible
that the fractionation procedure itself actually changes the ability to detect the
marker. In addition, when we restate results obtained for human leukemia, the
significance of transplantation of human cancer cells into SCID mice as an
indicator of a property of cancer stem cells has come into question (Kelly et al.,
2007). In contrast to the finding that only 1 in 250,000 human leukemic cells is
transplantable, essentially all of the cells of a mouse B-cell lymphoma will
produce tumors when injected into non-irradiated congenic recipients (Kelly
et al., 2007), a reiteration of a finding originally reported in 1937 (Furth and
Kahn, 1937). The possibility is thus raised that the tissue microenvironment of a
SCID mouse limits the ability of the human leukemic cells to form a tumor;
thus, the low fraction of transplantable cells in human leukemia could be due to
an incompatible microenvironment (Kelly et al., 2007).
The major question is whether cancer stem cells, or cancer cells in G 0 ,
responsible for the regrowth of cancer after treatment (Salmon, 1952) can be
isolated and purified. There are certainly some doubts about this. If they can, it
is possible that new therapies can be directed to the some specific characteristics
of the cancer stem cell (Sell, 2004b, 2006a, 2007a; Sell and Pierce, 1994; Reya
et al., 2001; Hill and Perris, 2007).
2.4 Differentiation Therapy
The ability of retinoids to induce differentiation of teratocarcinoma cells,
mentioned earlier, proves the principle that differentiation of cancer stem cells
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