Aquaporin 1 elicits cell motility and coordinates vascular bed formation by downregulating thrombospondin type-1 domain-containing 7A in glioblastoma
Aquaporin 1 elicits cell motility and coordinates vascular bed formation by downregulating thrombospondin type-1 domain-containing 7A in glioblastoma
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DOI：
10.1002/cam4.3032
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发表时间：
2020-06-01
期刊：
影响因子：
4
通讯作者：
Hayashi, Yasuhiko
中科院分区：
文献类型：
--
作者：
Oishi, Masahiro;Munesue, Seiichi;Hayashi, Yasuhiko
背景水通道蛋白（AQP）1表达与肿瘤恶性程度有关，但其在胶质母细胞瘤（GBM）（一种致命的胶质瘤）中的作用仍有待阐明。方法采用免疫组织化学方法检测33例人GBM中AQP1的表达。建立稳定表达AQP1的GBM细胞（U251和U87），并用于细胞增殖、迁移、侵袭和血管管形成测定。基因芯片检测用于鉴定AQP1表达细胞中差异表达的基因。结果AQP1仅在肿瘤细胞中表达。在GBM细胞系中，AQP1剂量依赖性地加速细胞迁移和侵袭，但不加速增殖。AQP1还上调组织蛋白酶B、粘着斑激酶和基质金属蛋白酶9的活性。GBM细胞中的AQP1以接触依赖的方式诱导ECV304血管内皮细胞的壁厚。在体外表达AQP1的GBM细胞中发现了血小板反应蛋白1型结构域7A（THSD7A）的下调，并与人GBM标本中AQP1的表达呈负相关。结论AQP1可能通过促进GBM细胞的迁移和侵袭，并通过下调THSD7A促进GBM特有的血管床形成，从而参与肿瘤的恶性发展。
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.