Aquaporin 1 elicits cell motility and coordinates vascular bed formation by downregulating thrombospondin type-1 domain-containing 7A in glioblastoma

Abstract

Background: Aquaporin (AQP) 1 expression has been linked with tumor malignancy but its role in glioblastoma (GBM), a lethal glioma, remains to be clarified. Methods: AQP1 expression was examined in 33 human GBM specimens by immunohistochemistry. GBM cells (U251 and U87) that stably express AQP1 were established and used for cellular proliferation, migration, invasion, and vascular tube formation assays. The GeneChip assay was used to identify differentially expressed genes in AQP1-expressing cells. Results: AQP1 was expressed only in tumor cells. AQP1 dose-dependently accelerated cell migration and invasion, but not proliferation, in GBM cell lines. AQP1 also upregulated cathepsin B, focal adhesion kinase and activities of matrix metalloproteinase 9. AQP1 in GBM cells induced wall thickness of ECV304, vascular endothelial cells, in a contact-dependent manner. Downregulation of thrombospondin type 1 domain containing 7A (THSD7A) was identified in AQP1-expressing GBM cells in vitro, and was negatively correlated with AQP1 expression in human GBM specimens. Conclusion: AQP1 is involved in tumor malignancy by facilitating the migration and invasion of GBM cells, and promoting the formation of vascular beds that are characteristic of GBM by downregulating THSD7A.