title: Novel animal glioma models that separately exhibit two different invasive and angiogenic phenotypes of human glioblastomas.
abstract: OBJECTIVE
  Invasive behaviors of malignant gliomas are fundamental traits and major reasons for treatment failure. Delineation of invasive growth is important in establishing treatment for gliomas and experimental neuro-oncology could benefit from an invasive glioma model. In this study, we established two new cell line-based animal models of invasive glioma.
  
  
  METHODS
  Two cell lines, J3T-1 and J3T-2, were derived from the same parental canine glioma cell line, J3T. These cells were inoculated to establish brain tumors in athymic mice and rats. Pathologic samples of these animal gliomas were examined to analyze invasive patterns in relation to angiogenesis, and were compared with human glioblastoma samples. The molecular profiles of these cell lines were also shown.
  
  
  RESULTS
  Histologically, J3T-1 and J3T-2 tumors exhibited different invasive patterns. J3T-1 cells clustered around newly developed vessels at tumor borders, whereas J3T-2 cells showed diffuse single cell infiltration into surrounding healthy parenchyma. In human malignant glioma samples, both types of invasion were observed concomitantly. Molecular profiles of these cell lines were analyzed by immunocytochemistry and with quantitative reverse transcription polymerase chain reaction. Vascular endothelial growth factor, matrix metalloproteinase-9, hypoxia-inducible factor-1, and platelet-derived growth factor were overexpressed in J3T-1 cells rather than in J3T-2 cells, whereas integrin αvβ3, matrix metalloproteinase-2, nestin, and secreted protein acidic and rich in cysteine were overexpressed in J3T-2 cells rather than in J3T-1 cells.
  
  
  CONCLUSIONS
  These animal models histologically recapitulated two invasive and angiogenic phenotypes, namely angiogenesis-dependent and angiogenesis-independent invasion, also observed in human glioblastoma. These cell lines provided a reproducible in vitro and in vivo system to analyze the mechanisms of invasion and angiogenesis in glioma progression.
authors: Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors: Satoshi
authors: S
authors: Inoue
authors: Tomotsugu
authors: T
authors: Ichikawa
authors: Kazuhiko
authors: K
authors: Kurozumi
authors: Tomoko
authors: T
authors: Maruo
authors: Manabu
authors: M
authors: Onishi
authors: Koichi
authors: K
authors: Yoshida
authors: Kentaro
authors: K
authors: Fujii
authors: Hirokazu
authors: H
authors: Kambara
authors: E Antonio
authors: EA
authors: Chiocca
authors: Isao
authors: I
authors: Date
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply / Q000503:physiopathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004285:Dogs; D005909:Glioblastoma / Q000098:blood supply / Q000503:physiopathology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000503:physiopathology; D010641:Phenotype; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude