Cornering Cancer Stem Cells
unique surface markers they bear...
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Techniques for sorting live cancer cells and for determining
A second crucial event in the evolution of cancer stem cell
whether they possess the ability to self-renew have led
studies was the advent during the 1990s of conclusive tests for
to the positive identifi cation of cancer stem cells within
self-renewal. Assays to establish self-renewal in human cells
larger cancer cell populations. In the cancers listed below,
did not exist until Weissman of Stanford and John E. Dick of
the malignant stem cells have been demonstrated capable
the University of Toronto developed methods that allowed
of self-renewal and able to regenerate the entire mixture
normal human stem cells to grow in mice. Using fl ow cytom-
of cell types found in the original tumor. Those properties
etry and this new mouse model, Dick began in 1994 to publish
mean that a small number of cancer stem cells could have
a series of seminal reports identifying cancer stem cells in leu-
given rise to the whole tumor, could continually replenish
kemia. In 2003 Richard Jones of Johns Hopkins University
its much larger cell population—the majority of which is
identifi ed a cancer stem cell population in multiple myeloma.
nontumorigenic—and could reconstitute the original cancer
Earlier the same year our own laboratory group at the Uni-
even if most or all of the tumor were destroyed. Eradicating
versity of Michigan at Ann Arbor had published the fi rst evi-
the disease would therefore require treatments to target
dence of cancer stem cells in solid tumors. By transplanting
the cancer stem cells successfully.
sorted populations of cells from human breast tumors into
CANCER T YPE (year cancer stem cells identified)
mice, we were able to confi rm that not all human breast cancer
Acute myeloid leukemia (1994)
cells have the same capacity to generate new tumor tissue.
Acute lymphoblastic leukemia (1997)
Only one subpopulation of the cells was able to re-create the
original tumor in the new environment. We then compared
Chronic myelogenous leukemia (1999)
the phenotype, or physical traits, of those new tumors with
Breast (2003)
that of the patient samples and found that the profi le of the
Multiple myeloma (2003)
new tumors recapitulated the original. This fi nding indicated
Brain (2004)
that the transplanted tumorigenic cells could both self-renew
Prostate (2005)
and give rise to all the different cell populations present in the
original tumor, including the nontumorigenic cells.
tion of stemlike cancer cells. The theory has a longer history,
Our study attested to the presence of a hierarchy of cells
but in the past the technology to prove it was lacking.
within a breast cancer similar to those identifi ed in blood ma-
By the 1960s a few scientists were already beginning to
lignancies. Since then, the investigation of cancer stem cell
note that groups of cells within the same tumor differed in
biology has exploded, as labs across the world continue to fi nd
their ability to produce new tumor tissue. In 1971 C. H. Park
similar subpopulations of tumorigenic cells in other forms of
and his colleagues at the University of Toronto showed that
cancer. In 2004, for example, the laboratory of Peter Dirks of
within a culture of cells taken from an original, or “primary,” the University of Toronto identifi ed cells from primary human myeloma (a cancer affecting plasma cells in bone marrow), the
central nervous system tumors with the capacity to regenerate
cells displayed signifi cant differences in their ability to prolif-
the entire tumor in mice. In addition, he found a high number
erate. At the time, Park’s group could not interpret this phe-
of the purported cancer stem cells present in one of the fastest-
nomenon decisively, because at least two explanations were
growing forms of human brain cancer, medulloblastoma,
possible: all the cells might have had the ability to multiply in
compared with far fewer tumorigenic cells found in less ag-
culture but by chance only some of them did, or else a hierar-
gressive brain tumor types.
