Annexin A2 regulates angiogenesis and invasion phenotypes of malignant glioma

• Published in: Brain tumor pathology 2015-07, Vol.32 (3), p.184-194
• Main Authors: Onishi, Manabu, Ichikawa, Tomotsugu, Kurozumi, Kazuhiko, Inoue, Satoshi, Maruo, Tomoko, Otani, Yoshihiro, Fujii, Kentaro, Ishida, Joji, Shimazu, Yosuke, Yoshida, Koichi, Michiue, Hiroyuki, Antonio Chiocca, E., Date, Isao
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Annexin A2 - genetics; Annexin A2 - physiology; Antibodies; Brain cancer; Brain Neoplasms - blood supply; Brain Neoplasms - genetics; Brain Neoplasms - pathology; Cancer Research; Cell adhesion & migration; Cell Adhesion - genetics; Cell culture; Cells, Cultured; Disease Models, Animal; Drinking water; Endothelial Cells; Female; Gene Expression; Glioma; Glioma - blood supply; Glioma - genetics; Glioma - pathology; Humans; Laboratories; Medicine; Medicine & Public Health; Neoplasm Invasiveness - genetics; Neovascularization, Pathologic - genetics; Neurology; Neurosurgery; Oncology; Original Article; Pathology; Penicillin; Platelet-Derived Growth Factor - metabolism; Proteins; Rats, Inbred F344; Thermal cycling; Tumors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 1433-7398; 1861-387X
• DOI: 10.1007/s10014-015-0216-6

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.