Boston College researchers build metastatic mouse model
CHESTNUTHILL, Mass.—Researchers at Boston College say they have developed the firstlaboratory mouse model that mimics metastatic cancer, theprimary cause of morbidity and mortality for cancer patients.
The development of the new mouse model may eliminate some researchhassles and enable scientists to more easily identify basic mechanisms andpotential new therapies to treat cancer, says project leader Dr. ThomasSeyfried, a Boston College biologist.
"The model is ideally suited for high-throughput in vivo and in vitro screening, and for identification of novel biomarkers andrelevant targets for cancer metastasis," he says.
Using a novel cell line, the Boston College team discovered that metastaticcells express properties of macrophages, tissue cells that usually protectorganisms against invading microbes in the environment and bacteria that leadto infection and disease.
"The key to our success in developing a natural mouse model ofsystemic metastatic cancer was the selection process we used to isolate themetastatic tumor cells," Seyfried says. "We employed an iterative in vivo selection process in theorthotopic tissue of the immunocompetent mouse host. This experimental strategyfacilitated enrichment of the most invasive and metastatic tumor cells. We werethen able to isolate, clone and engineer the cells with florescent andbioluminescent markers for in vivodetection."
Two of the cell lines, VM-M2 and VM-M3, expressedall of the major biological processes of metastasis, including local invasion,intravasation, immune system survival, extravasation and secondary tumorformation involving liver, kidney, spleen, lung and brain. The metastatic cellsexpressed properties of macrophages or macrophage-like cells, similar to thosereported previously in many types of human metastatic cancers.
The third cell line, VM-NM1, grew rapidly wheninjected into mice, but did not produce metastatic disease. Instead, theyexpressed properties of neural stem/progenitor cells.
This new VM tumor model will be useful forevaluating potential therapies for managing both metastatic and rapidly growingnon-metastatic tumors on a common immunocompetent genetic background, Seyfriedsays.
Seyfried points out that many existingmouse models fail to produce cancer in each animal subject, and it could takeseveral months before cancer is detected. In other models, cancer cells aretransplanted into animals with disabled immune systems. However, the researchteam was able to product tumors in all of the mice used in the study withinthree weeks, he says.
Seyfried says the research team hopes the major impact of itsdiscovery will be to enhance predictability of therapeutically effective drugsfor metastatic human cancers.
"This new model should greatly reduce the failure rate in cancerdrug development," he says.
Thestudy was funded by the American Institute of Cancer Research, the NationalInstitutes of Health and Boston College. The findings, reported in the online version of the International Journal of Cancer, werepresented during the annual meeting of the American Association of CancerResearch April 13 in San Diego.
Thenew models are available for license to researchers and pharmaceuticalcompanies through Boston College's Office for Technology Transfer andLicensing.