Expression and function of water channels (aquaporins) in migrating malignant astrocytes

Aquaporins (AQP) constitute the principal pathway for water movement across biological membranes. Consequently, their expression and function is important for cell volume regulation. Glioma cells quickly adjust their cell volume in response to osmotic challenges or spontaneously as they invade into the narrow and tortuous extracellular spaces of the brain. These cell volume changes are likely to engage water movements across the cell membrane through AQP. AQP expression in glioma cells is poorly understood. In this study, we examined the expression of AQP in several commonly used human glioma cell lines (D54, D65, STTG1, U87, U251) and in numerous acute patient biopsies by PCR, Western blot, and immunocytochemistry and compared them to nonmalignant astrocytes and normal brain. All glioma patient biopsies expressed AQP1, AQP4 and some expressed AQP5. However, when isolated and grown as cell lines they lose all AQP proteins except a few cell lines that maintain expression of AQP1 (D65, U251, GBM62). Reintroducing either AQP1 or AQP4 stably into glioma cell lines allowed us to show that each AQP is sufficient to restore water permeability. Yet, only the presence of AQP1, but not AQP4, enhanced cell growth and migration, typical properties of gliomas, while AQP4 enhanced cell adhesion suggesting differential biological roles for AQP1 and AQP4 in glioma cell biology.