Inhibition of the Sodium-Potassium-Chloride Cotransporter Isoform-1 reduces glioma invasion.

ABSTRACT: Malignant gliomas metastasize throughout the brain by infiltrative cell migration into peritumoral areas. Invading cells undergo profound changes in cell shape and volume as they navigate extracellular spaces along blood vessels and white matter tracts. Volume changes are aided by the concerted release of osmotically active ions, most notably K(+) and Cl(-). Their efflux through ion channels along with obligated water causes rapid cell shrinkage. Suitable ionic gradients must be established and maintained through the activity of ion transport systems. Here, we show that the Sodium-Potassium-Chloride Cotransporter Isoform-1 (NKCC1) provides the major pathway for Cl(-) accumulation in glioma cells. NKCC1 localizes to the leading edge of invading processes, and pharmacologic inhibition using

SUBMITTER: Haas BR 

PROVIDER: S-EPMC2896443 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature