(ChemotherapyAdvisor) – The mechanism by which tumor cells migrate in invasive glioblastoma involves the actions of the protein Na+-K+-Cl− cotransporter 1 (NKCC1), according to researchers of Johns Hopkins University, Baltimore, MD, and the University of Washington, Seattle, WA. This conclusion is based on a recent study entitled “Regulation of Brain Tumor Dispersal by NKCC1 through a Novel Role in Focal Adhesion Regulation,” which was published in PLoS Biology on May 1.
Glioblastoma, which is a highly invasive and lethal brain tumor due to its universal recurrence, has a poor prognosis. Previous studies suggest a role for NKCC1 in glioma cell migration and aggressiveness, but this role is poorly understood. For this study, the authors aimed to determine the precise role of NKCC1 in the invasiveness of human primary glioma cells in vitro and in vivo.
The investigators reported several lines of evidence for their conclusion. First, NKCC1 protein expression levels were significantly higher in glioblastoma and anaplastic astrocytoma tissues than in grade II glioma and normal cortex. Second, inhibition of NKCC1 expression led to decreased cell migration and invasion in vitro and in vivo. Finally, “epidermal growth factor, which promotes migration of glioma cells, increased the phosphorylation of NKCC1 through a PI3K-dependent mechanism. This finding is potentially related to WNK kinases.”
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The investigators concluded that “due to the ubiquitous expression of NKCC1 in mammalian tissues, its regulation by WNK kinases may serve as a new therapeutic target for glioblastoma aggressiveness and can be exploited by other highly invasive neoplasms.”
