Washington, Jan 5 (Inditop) Researchers led by an Indian American have developed a versatile mouse model of glioblastoma – the commonest of deadly brain cancers in humans.
“Mouse models of human cancer have taught us a great deal about the basic principles of cancer biology,” said Inder Verma, professor in the Laboratory of Genetics at the Salk Institute.
“By definition, however, they are just that: approximations that simulate a disease but never fully capture the molecular complexity underlying disease in humans.”
Verma received his Ph.D. from the Weizmann Institute of Science and was a postdoctoral fellow at MIT. He is an American Cancer Society professor of molecular biology and recipient of an NIH (National Institutes of Health) Outstanding Investigator award. Verma is the director of the Laboratory of Genetics at the Salk Institute.
Trying to mimic randomly occurring mutations that lie at the heart of all tumours, Salk Institute researchers used modified viruses to shuttle cancer-causing oncogenes into a handful of cells in adult mice.
This could not only prove very useful in faithfully reproducing different types of tumours but also to clarify the nature of elusive cancer stem cells.
The most frequently used mouse cancer model relies on xenografts: Human tumour tissue or cancer cell lines are transplanted in mice programmed to develop tumours quickly.
“These tumours are very reproducible, but this approach ignores the fact that the immune system can make or break cancer,” said co-author Tomotoshi Marumoto, former postdoctoral researcher in the Verma lab and now an assistant professor at the Kobe Medical Centre Hospital in Kobe, Japan.
Other animal models either express oncogenes in a tissue-specific manner or shut down the expression of tumour suppressor genes in the whole tissue.
“But we know that tumours generally develop from a single cell or a small number of cells of a specific cell type, which is one of the major determinants of the characteristics of tumour cells,” explained co-author Dinorah Friedmann-Morvinski.
To sidestep the shortcomings of currently used cancer models, the Salk team harnessed the power of lentiviral vectors to infect nondividing as well as dividing cells and ferry activated oncogenes into a small number of cells in adult, fully immunocompetent mice, said a Salk Institute release.
“These findings show that our cancer model will not only allow us to start understanding the biology of glioblastoma but will also allow us to answer many questions surrounding cancer stem cells,” said Verma.
Although the work described to date pertains to glioblastoma, Verma and his team are currently using this methodology to investigate lung, pancreatic, and pituitary cancers.
These findings were published in Sunday’s online issue of Nature Medicine.
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