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MBC in Press, published online ahead of print May 21, 2008
Mol. Biol. Cell 10.1091/mbc.E08-03-0319

A more recent version of this article appeared on August 1, 2008
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Submitted on March 26, 2008
Revised on May 6, 2008
Accepted on May 13, 2008

The Role of Myosin II in Glioma Invasion of the Brain

Christopher Beadle,*{dagger} Marcella C. Assanah,*{ddagger} Pascale Monzo,{sect} Richard Vallee,{sect} Steven S. Rosenfeld,{dagger}{ddagger} and Peter Canoll{ddagger}

Departments of {dagger}Neurology, {ddagger}Neurosurgery, and {sect}Cell Biology and Pathology, and the Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, NY 10032

Monitoring Editor: Erika Holzbaur

The ability of gliomas to invade brain limits the efficacy of standard therapies. In this study, we have examined glioma migration in living brain tissue using two novel in vivo model systems. Within brain, glioma cells migrate like nontransformed, neural progenitor cells—extending a prominent leading cytoplasmic process followed by a burst of forward movement by the cell body that requires myosin II. In contrast, on a two-dimensional surface, glioma cells migrate more like fibroblasts, and do not require myosin II to move. To explain this phenomenon, we studied glioma migration through a series of synthetic membranes with defined pore sizes. Our results demonstrate that the A and B isoforms of myosin II are specifically required when a glioma cell has to squeeze through pores smaller than its nuclear diameter. They support a model in which the neural progenitor-like mode of glioma invasion and the requirement for myosin II represent an adaptation needed to move within brain, which has a submicrometer effective pore size. Furthermore, the absolute requirement for myosin II in brain invasion underscores the importance of this molecular motor as a potential target for new anti-invasive therapies to treat malignant brain tumors.


*These authors contributed equally to this work.

Address correspondence to: Steven S. Rosenfeld (sr2327{at}columbia.edu)




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