Connexins and pannexins: Two gap junction families mediating glioma growth control

Abstract

Astrocytes are the most common glial cells found in the central nervous system (CNS). They are known to provide neurons with structural support and neurotrophic substances, as well as buffer the extracellular milieu and contribute to the blood-brain barrier (reviewed in Hatten et al., 1991). Unlike neurons, astrocytes can be readily induced to divide, and this may contribute to the formation of gliomas, which accounts for more than 65% of all primary brain tumors (Muller et al., 1977). However, since gliomas arise in the brain, therapeutic strategies including radiotherapy, chemotherapy, and complete surgical removal are often difficult to implement and pose a high risk of side effects to patients (Butowski et al., 2006). Moreover, invasive gliomas frequently relapse after treatments due to their extensive infiltration into surrounding tissues, consequently resulting in death in nearly all cases (Reardon et al., 2006). Therefore, exploring a more effective treatment for gliomas merits serious consideration. Targeting some of the cellular mechanisms controlling proliferation, migration, and invasion would constitute effective therapeutic strategies. One such mechanism involves intercellular communication through gap junctions. The current review will summarize the evidence supporting a role for gap junction channels and their constituent proteins in controlling cell proliferation and tumorigenesis in gliomas, focusing both on rodent models and, where applicable, human gliomas.