Scientists at the Johns
Hopkins Kimmel Cancer Center say they have evidence
that cancer stem
cells for multiple myeloma share many properties with
normal stem cells and have multiple ways of
resisting chemotherapy and other treatments.
A report on the evidence, published in the Jan. 1
issue of the journal Cancer Research, may
explain why the disease is so persistent, the Johns Hopkins
scientists say, and pave the way for
treatments that overcome the cells' drug resistance.
Multiple myeloma, which affects bone marrow and bone
tissue, is the second most common blood
cancer and strikes more than 14,000 Americans each year.
Close to 11,000 will die from the disease.
"Cancer stem cells that have distinct biology and drug
sensitivity as compared with the bulk of a
cancer may explain why multiple myeloma, like many other
cancers, so often relapses even after
chemotherapy puts patients into remission," said Richard J.
Jones, professor and director of bone
marrow transplant at Johns Hopkins' Kimmel Cancer Center
and one of the scientists who authored the
new report.
The existence of cancer stem cells--a topic of some
controversy in cancer biology--is seen by
some scientists as a useful explanation for the long
history of difficulty in overcoming some cancers'
persistence.
The Johns Hopkins investigators previously had
uncovered a rare stem cell in myeloma,
accounting for less than 1 percent of all the cancer's
cells. Working with cell samples from myeloma
patients, the team found that this stem cell originates
from immune system B-cells and is capable of
giving rise to the malignant bone marrow cells
characteristic of the disease.
In the current study, the scientists isolated stem
cells from the blood of four patients with
multiple myeloma and transplanted them into mice. All the
animals developed hind-limb paralysis and
showed signs of cancer in the bone marrow. By contrast,
plasma cells that were transplanted from
multiple myeloma patients to mice did not engraft. The
Johns Hopkins scientists say that re-creating
the disease in mice provides more evidence that these cells
act as cancer stem cells.
The Johns Hopkins scientists also compared the
response of these special stem cells with the
bulk of multiple myeloma plasma cells to four different
chemotherapy medications commonly used to
treat patients with the disease: dexamethasone,
lenadilomide, bortezomib and 4-
hydroxycyclophosphamide. While all four agents
significantly inhibited the growth of the plasma cells,
none inhibited the stem cells.
To their surprise, the researchers noted that the
multiple myeloma stem cells resemble other
types of adult stem cells and exhibit similar properties
that may make them resistant to
chemotherapy. They found that the stem cells contain high
levels of enzymes that neutralize toxins,
like cancer drugs, and expel them through miniature pumps
on their cell surface. The investigators
believe that these drug-fighting enzymes and pumps--also
plentiful in normal stem cells--may help
cancer stem cells resist treatment.
William Matsui, an assistant professor of oncology at
Johns Hopkins and the study's lead
investigator, said, "Nature made normal stem cells very
hearty for a reason, namely to survive and help
repair damaged tissues and organs after injury or illness.
To us, it makes sense that the same
processes that protect normal stem cells also exist in
cancer stem cells to make them resistant to
chemotherapy. We need to develop new ways to target the
specific biology of cancer stem cells to
prevent the continued production of mature tumor cells and
disease relapse."
"Standard cancer therapy is like mowing the weed--it
gets rid of the disease transiently, but
the dandelion always grows back," Jones said. "We need to
get rid of the root to cure disease and
therefore need a different type of therapy; mowing won't
work."
Matsui said the work also might make it possible to
track the rare myeloma stem cells as a
marker of how well a patient is doing during treatment.
The study was supported by the National Institutes of
Health, the American Society of Clinical
Oncology and the Pearse family. Additional participants in
the research were Qiuju Wang, James P.
Barber, Sarah Brennan, B. Douglas Smith, Ivan Borrello, Ian
McNiece, Lan Lin, Richard F. Ambinder,
Craig Peacock, D. Neil Watkins and Carol Ann Huff, all of
Johns Hopkins.
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