Astrocytes promote glioma invasion via the gap junction protein connexin43.

摘要: Reactive astrocytes are integral to the glioma microenvironment. Connexin43 (Cx43) is a major gap junction protein in and its expression enhanced significantly glioma-associated astrocytes, especially at peri-tumoral region. Although downregulation of Cx43-mediated intercellular communication associated with increased malignancy tumor cells, role Cx43 stromal cells progression not defined. Using mouse model consisting syngeneic intracranial implantation GL261 into Nestin-Cre:Cx43(fl/fl) mice where was eliminated we demonstrate astrocytic dissemination from core. To determine whether heterocellular between essential for reduced invasion absence Cx43, abolished channel formation by either knocking down short hairpin RNA (shRNA) or overexpressing dominant-negative channel-defective Cx43-T154A mutant these cells. Cx43shRNA invasion, had no effect on suggesting tumoral may influence motility independently function. Alteration function, such as replacing wild-type allele C-terminal truncated exhibiting coupling, sufficient reduce spreading brain parenchyma. Our results reveal novel an invasive niche raise possibility control manipulating