Annexin A2 regulates angiogenesis and invasion phenotypes of malignant glioma

作者：Onishi Manabu; Ichikawa Tomotsugu^*; Kurozumi Kazuhiko; Inoue Satoshi; Maruo Tomoko; Otani Yoshihiro; Fujii Kentaro; Ishida Joji; Shimazu Yosuke; Yoshida Koichi; Michiue Hiroyuki; Chiocca E Antonio; Date Isao

来源：Brain Tumor Pathology, 2015, 32(3): 184-194.

DOI：10.1007/s10014-015-0216-6

• Angiogenesis
• Animal model
• Annexin A2
• Glioma
• Invasion

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.

• 出版日期2015-7