Cryo Technique Enables Scientists to See Brain Tumor Cell Migration

For the first time, scientists can see pathways to stop a lethal brain cancer from spreading. Researchers have imaged individual cancer cells and the pathways they move as the tumor metastasizes. The researchers used an innovative cryoimaging technique to obtain the first-time look at a mouse model of glioblastoma multiforme (GBM), an especially aggressive cancer that has no treatments to stop it from metastasizing.

The study’s findings were published September 1, 2011, in the journal Cancer Research. “We’re able to see things we couldn’t before, and we can use these images to understand how tumor cells invade and disperse,” said Susann M. Brady-Kalnay, a professor of molecular biology and microbiology at the Case Western Reserve School of Medicine (Cleveland, OH, USA), and senior author of the study. That data, in turn, can be used to help develop and assess the effectiveness of drugs and other therapies used to treat the cancer, she said.

To obtain the view, the scientists used a model that included four different cell lines of brain cancers at various stages of tumor development and dispersion. The cancer cells were modified with fluorescent markers and implanted in the model’s brain in collaboration with biomedical engineering Prof. James Basilion’s lab. The cryoimaging system, developed by Dr. David Wilson, also a professor of biomedical engineering at Case Western Reserve, disassembles the brain layer by layer and reassembles the model into a color three-dimensional (3D) digital image.

Utilizing software and algorithms designed by the researchers, the scientists are able to differentiate the main tumor mass, the blood vessels that feed the cancer and dispersing cells. The imaging system enables them to peer at single cells and see exactly where they are in the brain. The lead researchers, Susan Burden-Gulley, Mohammed Qutaish, and Kristin Sullivant, found that two cell lines, a human brain cancer LN229, and a rodent cancer CNS-1, best resemble the actions of GBM in human patients.

Reconstructions of models of those two lines enabled the researchers to examine the extent and patterns of cancer cell migration and dispersal from tumors along blood vessels and white matter tracts within the brain. The ability to generate such clear and detailed images, according to the researchers, will be instrumental when evaluating the effectiveness of drugs and other therapies designed to block dispersal of glioblastoma multiforme cells.

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