Cancer Stem Cells
225
the minority population of CD34
+
CD38
cells was the only group of cells capable
of establishing human AML in the bone
marrow of Nonobese Diabetic Severe Com-
bined Immuno-deFciency (NOD/SCID)
mice. Within this population are also
Thy1
+
CD34
+
CD38
normal hematopoi-
etic stem cells (HSCs). Since leukemia-
initiating cells lack the Thy1 expression
characteristic of normal HSCs, it is likely
that while the early mutations occurred in
the HSC, the Fnal transforming mutations
occurred in early downstream progenitors
lacking Thy1 expression. An alternative
explanation is that Thy1 expression could
have been lost as a consequence of neo-
plastic transformation.
Tumorigenic
and
nontumorigenic
subsets of cancer cells have recently
been isolated from human breast cancer
tumors, providing the Frst conclusive
evidence for cancer stem cells in solid
tumors. Using a model for human breast
cancer similar to that used for AML, cells
were isolated, sorted by surface marker
expression using flow cytometry, and
grown in immunocompromised mice, as
sh
ownin±
ig
.1
.Am
in
o
r
i
t
yp
opu
l
a
t
ion
of
breast
cancer
cells
was
identiFed
in these tumors, which was exclusive
in
its
ability
to
form
new
tumors.
Tumorigenic cells could be distinguished
from nontumorigenic cancer cells based
upon surface-marker expression that was
consistent from patient to patient. In
eight out of nine patients, tumorigenic
cells could be prospectively identiFed and
isolated
as
CD44
+
CD24
/
low
Lineage
cells.
In
a
subset
of
these
tumors,
Epithelial SpeciFc Antigen (ESA) provided
further enrichment of the tumorigenic
population.
Limiting
dilution
assays
Primary tumor
Dissociate
cells
Flow
cytometry
CD44
or
CD24
+
and
lineage
CD44
+
CD24
flow
lineage
Inject into mice
No tumor growth;
cells are nontumorigenic
The tumor grows;
cells are tumorigenic
Fig. 1
Identifcation oF breast cancer tumorigenic cells.
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