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Mass. General study finds potential
ovarian cancer stem cells
Cells may underlie tumor recurrence
and resistance, suggest new treatment approaches
BOSTON - July 21, 2006 - Massachusetts General Hospital (MGH)
researchers have identified potential ovarian cancer stem cells,
which may be behind the difficulty of treating these tumors with
standard chemotherapy. Understanding more about the stem-like characteristics
of these cells could lead to new approaches to treating ovarian
cancer, which kills more than 16,000 U.S. women annually and is
their fifth most common cause of cancer death. The report will appear
in the July 25 Proceeding of the National Academy of Sciences
(PNAS) and has received early online release.
"We feel these stem-like cancer cells may be resistant to
traditional chemotherapy and could be responsible for the ultimately
fatal drug-resistant recurrence that is characteristic of ovarian
cancer," says Paul Szotek, MD, of the MGH
Pediatric Surgical Research Laboratories, first author of the
PNAS report. "We believe this likely is the first time
stem-like cells have been found in models of ovarian cancer and
in cells associated with human ovarian cancer."
Several recent studies have identified tiny populations of tumor
cells that appear to act like stem cells, driving the tumor's ability
to grow and spread. If some of these specialized cells escaped destruction
by chemotherapy or radiation, the tumor would be able to recur quickly,
often in a form resistant to chemotherapy. Similar cancer stem cells
have been previously identified in leukemia and breast cancer and
in cell lines of central nervous system and gastrointestinal tumors.
Standard treatment for ovarian cancer - surgical removal of all
involved tissues followed by chemotherapy - usually appears successful,
but treatment-resistant tumors recur in the vast majority of patients,
leading to a five-year survival rate of less than 30 percent. Those
factors and other observations suggested that cancer stem cells
may also be found with ovarian tumors, leading to the current study.
The MGH researchers first examined two mouse ovarian cancer cell
lines and identified cells with characteristics of the cancer stem
cells found with other tumors. They then observed a small percentage
of stem-like cells in human ovarian cancer lines and in cells taken
from ascites fluid that had accumulated within the abdomen of several
ovarian cancer patients. When mouse ovarian tumor stem-like cells
were injected under the skin of mice, they led to the formation
of new tumors much faster than did injections of regular tumor cells.
Although the potential ovarian cancer stem cells were less responsive
than regular tumor cells to in vitro treatment with the chemotherapy
drug doxorubicin, the stem-like cells remained sensitive to repeated
treatment with Mullerian Inhibiting Substance (MIS). This protein,
important in the normal development of sexual organs, has been studied
for its potential to treat several reproductive tumors by Patricia
Donahoe, MD, director of the MGH Pediatric Surgical Research Laboratories
and senior author of the PNAS study, and David MacLaughlin,
PhD, associate director of the labs and a study co-author.
"We feel that non-traditional, possibly innovative approaches
will be required to eradicate these stem-like cancer cells and ultimately
cure ovarian cancer. With its potential to maintain the ability
to inhibit the proliferation of these cells, MIS may play a role
in these new therapeutic approaches," Donahoe says. "We
intend to keep searching for stem-like cells in patient tumor samples
and to study their responsiveness to both chemotherapeutic agents
and to novel agents specifically targeted to stem cell as individualized
therapy of the future." Donahoe is the Marshall K. Bartlett
Professor of Surgery at Harvard Medical School.
Additional co-authors of the PNAS study are Rafael Pieretti-Vanmarcke,
MD, and Peter Masiakos, MD, MGH Pediatric Surgical Research Laboratories;
Rosemary Foster, PhD, MGH Hematology/Oncology; David Dombkowski,
and Frederic Preffer, PhD, MGH Center for Regenerative Medicine
and Harvard Stem Cell Institute; Daniela Dinulescu, PhD, Brigham
and Women's Hospital; and Denise Connolly, PhD, Fox Chase Cancer
Center, Philadelphia. The work was supported by the Ruth Kirchestin
National Research Service Award (T32 Cancer Biology Training Grant),
the Burroughs Wellcome Fund, the National Institutes of Health,
the U.S. Department of State, and contributions to the Pediatric
Surgical Research Laboratories from the McBride Family and the W.
Gerald Austen Funds.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of nearly $500 million and
major research centers in AIDS, cardiovascular research, cancer,
computational and integrative biology, cutaneous biology, human
genetics, medical imaging, neurodegenerative disorders, regenerative
medicine, transplantation biology and photomedicine. MGH and Brigham
and Women's Hospital are founding members of Partners HealthCare
HealthCare System, a Boston-based integrated health care delivery
system.
Media Contact: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
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