Stem cells make bone marrow cancer resistant to treatment
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
affects bone marrow and bone tissue.
"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," says Richard J. Jones, M.D., professor
and director of bone marrow transplant at 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 Hopkins investigators previously had uncovered a rare stem cell
in myeloma, accounting for less than one 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 of 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 Hopkins scientists say that recreating 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-hydroxycyclophosp
inhibited the growth of the plasma cells, none inhibited the stem
cells.
To their surprise, the research team 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.
"Nature made normal stem cells very hearty for a reason, namely to
survive and help repair damaged tissues and organs after injury or
illness," says William Matsui, M.D., an assistant professor of
oncology at Hopkins and the study's lead investigator. "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. We need to
get rid of the root to cure disease, and therefore need a different
type of therapy - mowing won't work," says Jones.
Matsui says the work also may make it possible to track the rare
myeloma stem cells as a marker of how well a patient is doing during
treatment.
Multiple myeloma 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.
###
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 from Johns Hopkins.
On the Web:
www.hopkinskimmelca
Public release date: 11-Jan-2008
Contact: Vanessa Wasta
wastava@jhmi.
410-955-1287
Johns Hopkins Medical Institutions
http://www.eurekale
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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