Role Of Aquaporin Water Channels In Cell Migration

Aquaporins (AQPs) are membrane water channels that play pivotal roles in physiological and pathophysiological processes in diverse mammalian organs. Thirteen mammalian AQP have been molecularly identified since AQP1 was first cloned from the membrane of erythrocyte in 1990. Recent studies uncovered an important role of aquaporins in cell migration, and migration-associated cell function such as angiogenesis, wound healing, and neutrophil motility, provided a new molecular mechanism of cell migration and opend a new field of aquaporin gene function .Migration of tumor cells is a crucial step in tumor invasion and metastasis. Previous studies demonstrated the expression of AQPs in many types of tumor cells. The role of aquaporins in tumor cell migration has not been reported. We hypothesize that aquaporins also play a critical role in tumor cell migration. Here we provide evidence that aquaporin expression is involved in tumor cell migration. RT-PCR, Immunofluorescence and Western blot analysis demonstrated AQP1 protein expression on the plasma membrane of SMMC-7221 human hepatoma cells. SMMC-7221 cell clones with high (SMMC-7221hPf) and low (SMMC-7221lPf) water permeability were identified by functional assays with corresponding high and low AQP1 expression. Cell migration rate was remarkably higher in SMMC-7221hPf cells as compared to SMMC-7221lPf cells, assessed by Boyden chamber and wound healing assays, whereas cell growth and adhesion were not different. Adenovirus-mediated AQP1 expression in SMMC-7221lPf cells increased their water permeability and migration rate. These results provide the first evidence that aquaporin-mediated membrane water permeability enhances tumor cell migration and may be associated with tumor invasion and metastasis.To further investigate the functions of aquaporin water channels in cell migration, we established the transgenic mouse model expressing the fluorescent protein EYFP-V163S sensitive to Cl-. The establishment of EYFP-V163S transgenic mouse model will bring it into realization that measure directly water and Cl- channel function in different tissues by perfusing in vivo tissues with halides and detecting dynamically the change of fluorescent. At the same time, cells from tissues of EYFP-V163S transgenic mouse could be cultured as cell models for studing the roles of aquaporin water channels in cell migration.