title: Annexin A2 regulates angiogenesis and invasion phenotypes of malignant glioma.
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.
authors.affiliation: Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikatacho, Kitaku, Okayama, 700-8558, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Onishi
authors.forename: Tomotsugu
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kurozumi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
authors.forename: Tomoko
authors.initials: T
authors.lastname: Maruo
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Otani
authors.forename: Kentaro
authors.initials: K
authors.lastname: Fujii
authors.forename: Joji
authors.initials: J
authors.lastname: Ishida
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Shimazu
authors.forename: Koichi
authors.initials: K
authors.lastname: Yoshida
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Michiue
authors.forename: E
authors.initials: E
authors.lastname: Antonio Chiocca
authors.forename: Isao
authors.initials: I
authors.lastname: Date
mesh_terms: D000818:Animals; D017306:Annexin A2 / Q000235:genetics / Q000502:physiology*; D001932:Brain Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000473:pathology*; D002448:Cell Adhesion / Q000235:genetics; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells; D005260:Female; D015870:Gene Expression; D005910:Glioma / Q000098:blood supply / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011916:Rats, Inbred F344; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D017306:Annexin A2; D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; C075278:platelet-derived growth factor A