Novel animal glioma models that separately exhibit two different invasive and angiogenic phenotypes of human glioblastomas

Satoshi Inoue, Tomotsugu Ichikawa, Kazuhiko Kurozumi, Tomoko Maruo, Manabu Onishi, Koichi Yoshida, Kentaro Fujii, Hirokazu Kambara, E. Antonio Chiocca, Isao Date

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)670-682
Number of pages13
JournalWorld Neurosurgery
Volume78
Issue number6
DOIs
Publication statusPublished - Dec 2012

Fingerprint

Glioblastoma
Glioma
Animal Models
Phenotype
Cell Line
Nude Rats
Hypoxia-Inducible Factor 1
Nestin
Matrix Metalloproteinase 2
Platelet-Derived Growth Factor
Matrix Metalloproteinase 9
Treatment Failure
Nude Mice
Integrins
Brain Neoplasms
Vascular Endothelial Growth Factor A
Reverse Transcription
Cysteine
Canidae
Neoplasms

Keywords

  • Angiogenesis
  • Animal brain tumor model
  • Glioma
  • Invasion

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery

Cite this

Novel animal glioma models that separately exhibit two different invasive and angiogenic phenotypes of human glioblastomas. / Inoue, Satoshi; Ichikawa, Tomotsugu; Kurozumi, Kazuhiko; Maruo, Tomoko; Onishi, Manabu; Yoshida, Koichi; Fujii, Kentaro; Kambara, Hirokazu; Chiocca, E. Antonio; Date, Isao.

In: World Neurosurgery, Vol. 78, No. 6, 12.2012, p. 670-682.

Research output: Contribution to journalArticle

Inoue, Satoshi ; Ichikawa, Tomotsugu ; Kurozumi, Kazuhiko ; Maruo, Tomoko ; Onishi, Manabu ; Yoshida, Koichi ; Fujii, Kentaro ; Kambara, Hirokazu ; Chiocca, E. Antonio ; Date, Isao. / Novel animal glioma models that separately exhibit two different invasive and angiogenic phenotypes of human glioblastomas. In: World Neurosurgery. 2012 ; Vol. 78, No. 6. pp. 670-682.
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AU - Ichikawa, Tomotsugu

AU - Kurozumi, Kazuhiko

AU - Maruo, Tomoko

AU - Onishi, Manabu

AU - Yoshida, Koichi

AU - Fujii, Kentaro

AU - Kambara, Hirokazu

AU - Chiocca, E. Antonio

AU - Date, Isao

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AB - 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.

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