Cancer Stem Cells
223
Presently, therapeutic targets are selected on the basis of the assumption that all of
the cancer cells within a particular tumor are equivalent in that they are all capable
of driving tumorigenesis and metastasis. New data suggests that, in at least some
cancers, a small, phenotypically distinct subset of the cancer cells (tumorigenic cells,
or cancer stem cells) has the exclusive ability to form tumors. The rest of the cells,
which form the bulk of the tumor, are unable to self-renew or sustain tumorigenesis.
Tumorigenic and nontumorigenic cancer cells can be identiFed on the basis of
cell surface-marker expression, utilizing the same tools used in normal stem cell
biology. This suggests that therapies could be made more effective by targeting the
tumorigenic cell population. The ability to identify tumorigenic cancer cells should
therefore allow the identiFcation of new diagnostic markers and therapeutic targets,
better evaluation of candidate therapeutics, and more accurate determination of
therapeutic efFcacy.
1
Introduction
Most tissues in which common cancers
arise contain a subpopulation of pro-
liferating cells that are responsible for
replenishing the short-lived mature cells
as they undergo apoptosis or are otherwise
damaged. Cell maturation is arranged in a
hierarchy in which this rare subpopulation
of stem cells give rise to progenitor cells
and eventually mature cells; the stem cell
pool replenishes itself through a process
called
self-renewal
.
Recent discoveries indicated that it is
likely that the tumors contain a minority
‘‘cancer stem cell’’ population with indef-
inite proliferative potential that drives the
growth and metastasis of tumors. ±urther-
more, emerging evidence suggests that
similar molecular mechanisms regulate
self-renewal in normal stem cells and their
malignant counterparts. If this is true, a
more complete understanding of the cellu-
lar biology of the tissues in which cancers
arise, and speciFcally of the stem cells
residing in those tissues, could provide
new insights into cancer biology. Certain
aspects of stem cell biology apply to cancer.
±irst, both normal stem cells and cancer
stem cells undergo self-renewal – a prop-
erty that separates them from the bulk of
normal tissue cells and the bulk of tu-
mor cells, respectively. Additionally, it is
quite likely that mutations that lead to
cancer accumulate in normal stem cells
since they are the only long-lived cells in
many tissues.
2
Evidence for Cancer Stem Cells
2.1
Viewing a Tumor as an Abnormal Organ
Cancers consist of phenotypically hetero-
geneous populations of cancer cells. These
phenotypically distinct cell populations
could arise, in part, from sequential mu-
tations occurring because of either genetic
instability and/or environmental factors.
Another possible source of this hetero-
geneity becomes apparent if one views a
tum
o
ra
sana
b
e
r
r
an
to
r
g
anc
on
t
a
in
in
g
a tumorigenic (stem cell) population that
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