Glioma Cells Self-organize Into Streams of Cells That Follow a Mathematically Predicted Pattern to Build Brain Tumors

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New research indicates that brain tumor cells can self-organize.
New research indicates that brain tumor cells can self-organize.

SAN DIEGO, CA­—Brain tumor cells can self-organize, according to new research presented at 2015 Cell Biology, the American Society for Cell Biology (ASCB) annual meeting.

In brain cancer, glioma cells build tumors by self-organizing into streams 10 to 20 cells wide that obey a mathematically predicted pattern for autonomous agents flowing together. These streams drag along slower gliomas, may block entry of immune cells, and swirl around a central axis containing glioma stem cells that promote tumor growth.

Researchers Pedro Lowenstein, MD, PhD, Sebastien Motsch, PhD, and colleagues at the University of Michigan and Arizona State University mapped out this dynamic picture of glioma self-organization by building and comparing two model systems: one biological and one mathematical. The biological model system was built in vivo using mouse and human glioma cells genetically tailored to express a package of genes known to spur development and progression of brain tumors.

The movement, distribution, and invasive nature of the resulting streams of elliptically shaped glioma cells were predicted by the researchers' mathematical model. Assuming the glioma cells were independent agents, the mathematical model considered adhesion and repulsion dynamics between tumor cells. The results showed unmistakable signs of nonrandom, self-organization of brain tumors, reported Lowenstein and Motsch.

The presence of self-organizing structures was not related to any specific cancer mutation. These swirls eddied around cores of glioma stem cells Lowenstein and Motsch describe as possible nucleating centers for brain tumor growth. The in vivo model also produced glioma cells organized as individual spheres, including some that slipped out of the tumor and set themselves adrift in the cerebrospinal fluid surrounding the brain's ventricles, and may mediate tumor dispersion throughout the brain.

All this evident self-organization opens an exciting novel insight into brain cancer, said Lowenstein and Motsch, and makes disrupting tumor self-organization itself a new target for brain cancer treatment.

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