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 AQ...

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Main Authors: Masahiro Oishi, Seiichi Munesue, Ai Harashima, Mitsutoshi Nakada, Yasuhiko Yamamoto, Yasuhiko Hayashi
Format: Article
Language:English
Published: Wiley 2020-06-01
Series:Cancer Medicine
Subjects:
Online Access:https://doi.org/10.1002/cam4.3032
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author Masahiro Oishi
Seiichi Munesue
Ai Harashima
Mitsutoshi Nakada
Yasuhiko Yamamoto
Yasuhiko Hayashi
author_facet Masahiro Oishi
Seiichi Munesue
Ai Harashima
Mitsutoshi Nakada
Yasuhiko Yamamoto
Yasuhiko Hayashi
author_sort Masahiro Oishi
collection DOAJ
description 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.
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spelling doaj.art-b1e0fb140e6140b0b61152b1688f6fd72022-12-22T02:05:06ZengWileyCancer Medicine2045-76342020-06-019113904391710.1002/cam4.3032Aquaporin 1 elicits cell motility and coordinates vascular bed formation by downregulating thrombospondin type‐1 domain‐containing 7A in glioblastomaMasahiro Oishi0Seiichi Munesue1Ai Harashima2Mitsutoshi Nakada3Yasuhiko Yamamoto4Yasuhiko Hayashi5Department of Neurosurgery Kanazawa University Graduate School of Medical Sciences Kanazawa JapanDepartment of Biochemistry and Molecular Vascular Biology Kanazawa University Graduate School of Medical Sciences Kanazawa JapanDepartment of Biochemistry and Molecular Vascular Biology Kanazawa University Graduate School of Medical Sciences Kanazawa JapanDepartment of Neurosurgery Kanazawa University Graduate School of Medical Sciences Kanazawa JapanDepartment of Biochemistry and Molecular Vascular Biology Kanazawa University Graduate School of Medical Sciences Kanazawa JapanDepartment of Neurosurgery Kanazawa University Graduate School of Medical Sciences Kanazawa JapanAbstract 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.https://doi.org/10.1002/cam4.3032aquaporin‐1glioblastomaTHSD7Atube formationvascular bed
spellingShingle Masahiro Oishi
Seiichi Munesue
Ai Harashima
Mitsutoshi Nakada
Yasuhiko Yamamoto
Yasuhiko Hayashi
Aquaporin 1 elicits cell motility and coordinates vascular bed formation by downregulating thrombospondin type‐1 domain‐containing 7A in glioblastoma
Cancer Medicine
aquaporin‐1
glioblastoma
THSD7A
tube formation
vascular bed
title Aquaporin 1 elicits cell motility and coordinates vascular bed formation by downregulating thrombospondin type‐1 domain‐containing 7A in glioblastoma
title_full Aquaporin 1 elicits cell motility and coordinates vascular bed formation by downregulating thrombospondin type‐1 domain‐containing 7A in glioblastoma
title_fullStr Aquaporin 1 elicits cell motility and coordinates vascular bed formation by downregulating thrombospondin type‐1 domain‐containing 7A in glioblastoma
title_full_unstemmed Aquaporin 1 elicits cell motility and coordinates vascular bed formation by downregulating thrombospondin type‐1 domain‐containing 7A in glioblastoma
title_short Aquaporin 1 elicits cell motility and coordinates vascular bed formation by downregulating thrombospondin type‐1 domain‐containing 7A in glioblastoma
title_sort aquaporin 1 elicits cell motility and coordinates vascular bed formation by downregulating thrombospondin type 1 domain containing 7a in glioblastoma
topic aquaporin‐1
glioblastoma
THSD7A
tube formation
vascular bed
url https://doi.org/10.1002/cam4.3032
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