Although genetic mutations are usually responsible for the initial tumor formation and progression, changes in the microenvironment also have a critical role in facilitating this process. Many ''untransformed'' cells infiltrate the tumors, and recent evidence suggests cancer cells can ‘reprogram’ normal cells by miRNAs, which are small, non-coding RNA molecules that regulate several protein targets. One prominent feature of glioma pathology is massive gliosis, an inflammatory response consisting of reactive astrocytes, in and around the tumor. We show that expression of Cx43, a major gap junction protein in astrocytes, is significantly enhanced in astrocytes at the tumor border. Using a mouse model consisting of syngeneic intracranial implantation of GL261 glioma cells into Nestin-Cre:Cx43fl/fl mice in which Cx43 is selectively eliminated in astrocytes, we demonstrate that reduction of astrocytic Cx43 decreases the dissemination of glioma cells from the tumor core. Similarly, knocking down Cx43 in astrocytes also reduces glioma invasion in a co-culture of glioma cells and astrocytes. By comparing the microRNA profiles of the astrocytes before and after co-culture with human glioma cells, we have identified a miR-5096 that appears to reprogram astrocytes to enhance the invasiveness of glioma cells. We are now examining whether we can prevent glioma cells from invading the brain and establishing recurrent secondary tumors by stopping the exchange of materials between glioma cells and astrocytes through eliminating Cx43 channel activity.