The propensity of glioma cells to invade brain is a vexing problem that limits the effectiveness of all current therapies. Thus, there remains a pressing need to identify new anti-invasive strategies. Accomplishing this will require a detailed understanding of how glioma cells migrate within the brain, and what machinery they use to drive this process. In our earlier work, we determined that the molecular motor myosin II plays an indispensable role in glioma dispersion through brain. However, fundamental questions about this process remain unanswered. First, how do myosin IIA and IIB, the two myosin II isoforms commonly expressed in gliomas, execute the processes underlying brain invasion? Second, how do signal transduction pathways that are frequently dysregulated in gliomas affect the functions of these myosin II isoforms and how redundant are these pathways in stimulating myosin II-dependent tumor invasion? Finally, how do myosin IIA and IIB function contribute to the dispersion of gliomas in tumor-bearing animals? The experiments described in this proposal will explore the advantages and potential limitations of one anti-invasive approach that targets a key element in the machinery gliomas use to invade brain--myosin II.
Glioma cells have a remarkable capacity to diffusely infiltrate the brain, limiting the effectiveness of current therapies. Our preliminary results show that the molecular motor myosin II plays an essential role in this process. The goals of this study is to critically examine how myosin II drives the process of glioma dispersion and explore ways in which it can be specifically and effectively targeted.
| Ivkovic, Sanja; Beadle, Christopher; Noticewala, Sonal et al. (2012) Direct inhibition of myosin II effectively blocks glioma invasion in the presence of multiple motogens. Mol Biol Cell 23:533-42 |
| Lei, Liang; Sonabend, Adam M; Guarnieri, Paolo et al. (2011) Glioblastoma models reveal the connection between adult glial progenitors and the proneural phenotype. PLoS One 6:e20041 |
