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Annexin A2 regulates angiogenesis and invasion phenotypes of malignant glioma.

Brain tumor pathology (2015-02-24)
Manabu Onishi, Tomotsugu Ichikawa, Kazuhiko Kurozumi, Satoshi Inoue, Tomoko Maruo, Yoshihiro Otani, Kentaro Fujii, Joji Ishida, Yosuke Shimazu, Koichi Yoshida, Hiroyuki Michiue, E Antonio Chiocca, Isao Date
ABSTRACT

We have established a pair of animal models (J3T-1 and J3T-2) with different invasive and angiogenic phenotypes, and demonstrated that annexin A2 is expressed at higher levels in J3T-1 than J3T-2 cells. The function of annexin A2 in relation to angiogenesis and invasion was investigated using these models. Stable silencing or overexpression of annexin A2 in J3T-1 and J3T-2 cells (J3T-1shA and J3T-2A cells) was established and used. Thirty human glioblastoma samples were evaluated for expression of annexin A2, vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). Immunohistochemical and quantitative reverse-transcription polymerase chain reaction analyses revealed higher expression of annexin A2, VEGF and PDGF in J3T-1 and J3T-2A cells. Cultured J3T-1 and J3T-2A cells exhibited higher adhesive ability to endothelial cells. Histopathological analysis of animal brain tumors revealed that J3T-1 and J3T-2A tumors displayed marked angiogenesis and invasion along the neovasculature, whereas J3T-2 and J3T-1shA tumors exhibited diffuse, infiltrative invasion without angiogenesis. Positive expression of annexin A2 was observed in tumor cells surrounding dilated vessels in 25/30 human glioblastoma specimens. Our results reveal that the phenotype of glioma invasion is closely related to angiogenesis. We identify annexin A2 as a factor regulating angiogenesis and invasion of malignant gliomas.

MATERIALS
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Solketal methacrylate, 50 wt. % in dichloromethane, contains ~280 ppm 4-tert-butylcatechol as inhibitor
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MISSION® esiRNA, targeting human ANXA2
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