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 Boston College researchers build metastatic mouse model
04-23-2008
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CHESTNUT
HILL, Mass.—Researchers at Boston College say they have developed the first
laboratory mouse model that mimics metastatic cancer, the
primary cause of morbidity and mortality for cancer patients.
The development of the new mouse model may eliminate some research
hassles and enable scientists to more easily identify basic mechanisms and
potential new therapies to treat cancer, says project leader Dr. Thomas
Seyfried, a Boston College biologist.
“The model is ideally suited for high-throughput in vivo and in vitro screening, and for identification of novel biomarkers and
relevant targets for cancer metastasis,” he says.
Using a novel cell line, the Boston College team discovered that metastatic
cells express properties of macrophages, tissue cells that usually protect
organisms against invading microbes in the environment and bacteria that lead
to infection and disease.
“The key to our success in developing a natural mouse model of
systemic metastatic cancer was the selection process we used to isolate the
metastatic tumor cells,” Seyfried says. “We employed an iterative in vivo selection process in the
orthotopic tissue of the immunocompetent mouse host. This experimental strategy
facilitated enrichment of the most invasive and metastatic tumor cells. We were
then able to isolate, clone and engineer the cells with florescent and
bioluminescent markers for in vivo
detection.”
Two of the cell lines, VM-M2 and VM-M3, expressed
all of the major biological processes of metastasis, including local invasion,
intravasation, immune system survival, extravasation and secondary tumor
formation involving liver, kidney, spleen, lung and brain. The metastatic cells
expressed properties of macrophages or macrophage-like cells, similar to those
reported previously in many types of human metastatic cancers.
The third cell line, VM-NM1, grew rapidly when
injected into mice, but did not produce metastatic disease. Instead, they
expressed properties of neural stem/progenitor cells.
This new VM tumor model will be useful for
evaluating potential therapies for managing both metastatic and rapidly growing
non-metastatic tumors on a common immunocompetent genetic background, Seyfried
says.
Seyfried points out that many existing
mouse models fail to produce cancer in each animal subject, and it could take
several months before cancer is detected. In other models, cancer cells are
transplanted into animals with disabled immune systems. However, the research
team was able to product tumors in all of the mice used in the study within
three weeks, he says.
Seyfried says the research team hopes the major impact of its
discovery will be to enhance predictability of therapeutically effective drugs
for metastatic human cancers.
“This new model should greatly reduce the failure rate in cancer
drug development,” he says.
The
study was funded by the American Institute of Cancer Research, the National
Institutes of Health and Boston College. The findings, reported in the online version of the International Journal of Cancer, were
presented during the annual meeting of the American Association of Cancer
Research April 13 in San Diego.
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