The Role Of AQP4 In The Deve Opment Of Glioblastoma

Glioblastoma multiforme (GBM), also known as glioblastoma and grade IV astrocytoma, is the most common and most aggressive brain tumor in human.There is no clear way to prevent the disease. Typically treatment involves surgery after which chemotherapy and radiation therapy is used. Despite maximum treatment, the cancer usually recurs. The most common length of survival after treatment is one year.Cancer stem cells (CSCs) were found in GBM, called glioma stem cells (GSCs). Glioma stem cells are phenotypically similar to the normal stem cells, they possess the self-renewal potential. Glioma stem cells are capable recapitulate original polyclonal tumors when xenografted to nude mice. They are radioresistant and chemoresistant, which eventually results in tumor recurrence after conventional glioblastoma therapy. Targeting GSCs for treatment is the most crucial issue. Targeting GSCs by eliminating the GBM tumor may provide an innovative way to reduce tumor recurrence by providing a synergistic effect with conventional treatment. The combination of conventional surgery, chemotherapy, and radiotherapy with stem cell-orientated therapy may provide a new promising treatment for reducing GBM recurrence and improving the survival rate.Aquaporion 4 (AQP4) is a protein which in human is encoded by the AQP4 gene. AQP4 belongs to the aquaporin family of integral membrane proteins that conduct water through the cell membrane. AQP4 plays a key role in maintaining water and ion homeostasis in central nervous system (CNS). AQP4 also involves in cell migration and neuroexcitation. The expression of AQP4 is increased in glioblastoma.The data of GBM patients was downloaded from TCGA and the relationship between AQP4 expression and the survival time of patients was analyzed. The result showed that high expression of AQP4 associated with short survival time. We supposed that AQP4 might involve in the process of glioblastoma. We found that the expression of AQP4 in glioma stem cells was significantly higher compared with normal nerve stem cells.All the evidences suggested that AQP4 might play a role in glioma stem cells.We used shRNA to suppress the expression of AQP4 in glioma stem cells to test the hypothesis that AQP4 played a role in maintaining the fundamental properties of GSC.In the present study, we showed that AQP4 knockdown altered the status of glioma stem cells. AQP4 knockdown inhibited proliferation, migration and self-renewal of GSC in vitro. Xenograft experiment revealed that AQP4 knockdown impaired the ability of tumorigenesis of GSC in vivo.Our study demonstrates that AQP4 might be involved in the proliferation, survival, migration, self-renewal and tumorigenesis of GSC. AQP4 might be a target gene in GSC function inhibition and GBM treatment.