| Description |
A characteristic pathological feature of malignant glioma cells is their ability to extensively invade surrounding brain parenchyma-particularly along white matter tracts- thus rendering focal therapies incapable of controlling tumor growth and resulting in inevitable recurrence. In this regard, identification of factors responsible for such invasion has become a central theme in glioma research, and elucidation of intracellular signal transduction systems and regulatory mechanisms important for controlling the process of invasion are of great clinical interest. In the article by Kubiatowski, et al., in this issue (Kubiatowski T, Jang T, Lachyankar MB, et al: Association of increased phosphatidylinositol 3-kinase signaling with increased invasiveness and gelatinase activity in malignant gliomas. J Neurosurg 95:480-488, September, 2001), the authors have demonstrated that increased phosphatidylinositol 3-kinase (PI3-K) activity correlates with Akt phosphorylation and also increased matrix metalloproteinase (MMP)-2 and -9 production. Matrix metalloproteinases are fundamentally involved with proteolytic degradation of the extracellular matrix (gelatin), a preliminary step in the invasion process.6 The increased MMP-2/-9 production associated with PI3-K activity correlates with invasion through matrigel, as demonstrated in this study. Pharmacological inhibition of PI3-K activity byWortmannin and LY294002 decreases invasion of glioma cells, suggesting that targeting of this pathway is of potential therapeutic importance. |
