ROCKs are expressed in brain tumors and are required for glioma-cell migration on myelinated axons

Patrick Oellers1, Uwe Schröer, Volker Senner

  • 1Department of Experimental Ophthalmology, School of Medicine, University Eye Hospital Münster, Domagkstrasse 15, Münster, Germany.

Glia
|September 25, 2008
PubMed

Insights

Glioma cells migrate along myelinated axons via Rho GTPases and Rho-associated kinases (ROCKs). This migration is faster than on laminin-1 and is specifically blocked by ROCK inhibitors, suggesting unique mechanisms.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Oncology

Background:

  • Glioma cell migration is critical for tumor progression.
  • The interaction between glioma cells and the brain's white matter tracts is not well understood.
  • Myelinated axons form the brain's white matter tracts.

Purpose of the Study:

  • To investigate the mechanisms of glioma cell migration along myelinated axons.
  • To determine the role of Rho GTPases and Rho-associated kinases (ROCKs) in this process.
  • To compare glioma cell migration on myelinated axons versus extracellular matrix proteins.

Main Methods:

  • Developed a novel coculture system of C6 glioma cells and chicken retinal axons.
  • Assessed the expression of Rho GTPases and ROCKs in migrating glioma cells.
  • Quantified glioma cell migration rates in vitro.
  • Utilized the ROCK inhibitor Y27632 to block specific pathways.

Main Results:

  • C6 glioma cells migrated along myelinated chicken retinal axons.
  • Glioma cells expressed Rho GTPases and ROCKs during migration.
  • ROCK1 isoform was highly expressed in human high-grade gliomas.
  • Migration along myelinated axons was faster than on laminin-1.
  • ROCK inhibition specifically blocked migration on myelinated axons but not on laminin-1.

Conclusions:

  • Glioma cell migration along myelinated axons involves distinct molecular mechanisms compared to migration on extracellular matrix.
  • Rho GTPases and ROCK signaling, particularly ROCK1, play a significant role in glioma cell navigation along white matter tracts.
  • These findings offer potential therapeutic targets for inhibiting glioma invasion.