Contribution of gap junctional communication between tumor cells and astroglia to the invasion of the brain parenchyma by human glioblastomas.

摘要: Gliomas are "intraparenchymally metastatic" tumors, invading the brain in a non-destructive way that suggests cooperation between glioma cells and their environment. Recent studies using an engineered rodent C6 tumor cell line have pointed to mechanisms of invasion involved gap junctional communication (GJC), with connexin 43 as substrate. We explored whether this concept may clinical relevance by analyzing participation GJC human glioblastoma invasion. Three complementary vitro assays were used: (i) seeding on collagen IV, analyze homocellular interactions (ii) co-cultures astrocytes, study glioblastoma/astrocytes relationships (iii) implantation into organotypic slice cultures, mimic three-dimensional parenchymal Carbenoxolone, potent blocker GJC, inhibited migration two latter models. It paradoxically increased it first one. These results showed interaction supports intercellular adhesion, whereas heterocellular through functional conversely support migration. As demonstrated for line, be responsible coupling. Its levels expression, high correlated positively invasiveness biopsied tumors. our underscore potential put forward other authors based experiments use astrocytes substrate subverting 43-dependent junctions.