Boston College researchers build metastatic mouse model
CHESTNUT HILL, Mass.óResearchers 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.