The Role of Myosin II in Glioma Invasion of the Brain
Myosin Type II
0303 health sciences
Brain Neoplasms
Green Fluorescent Proteins
Brain
Glioma
Fibroblasts
Models, Biological
Rats
Gene Expression Regulation, Neoplastic
Rats, Sprague-Dawley
03 medical and health sciences
Cell Movement
Animals
Humans
Electrophoresis, Gel, Two-Dimensional
Neoplasm Transplantation
DOI:
10.1091/mbc.e08-03-0319
Publication Date:
2008-05-22T01:23:01Z
AUTHORS (6)
ABSTRACT
The ability of gliomas to invade the brain limits the efficacy of standard therapies. In this study, we have examined glioma migration in living brain tissue by using two novel in vivo model systems. Within the 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 they 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 the 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.
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