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Annexin A2 regulates angiogenesis and invasion phenotypes of malignant glioma

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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.

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Acknowledgments

We thank M. Arao, A. Ishikawa and N. Uemori for their technical assistance. The following medical students also contributed to the animal experiments: T. Mifune, S. Murai, M. Matsueda, H. Matsumoto and Y. Yoshida. This study was supported by Grants-in-aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology to T.I. (No. 19591675; No. 22591611) and K.K. (No. 20890133; No. 21791364).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikatacho, Kitaku, Okayama, 700-8558, Japan

    Manabu Onishi, Tomotsugu Ichikawa, Kazuhiko Kurozumi, Satoshi Inoue, Tomoko Maruo, Yoshihiro Otani, Kentaro Fujii, Joji Ishida, Yosuke Shimazu, Koichi Yoshida, Hiroyuki Michiue & Isao Date

  2. Department of Neurosurgery, Brigham and Women’s/Faulkner Hospital, 75 Francis Street, Boston, MA, 02116, USA

    E. Antonio Chiocca

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  1. Manabu Onishi
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  2. Tomotsugu Ichikawa
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  3. Kazuhiko Kurozumi
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  4. Satoshi Inoue
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  13. Isao Date
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Correspondence to Tomotsugu Ichikawa.

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Onishi, M., Ichikawa, T., Kurozumi, K. et al. Annexin A2 regulates angiogenesis and invasion phenotypes of malignant glioma. Brain Tumor Pathol 32, 184–194 (2015). https://doi.org/10.1007/s10014-015-0216-6

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  • DOI: https://doi.org/10.1007/s10014-015-0216-6

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