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Peptide-based inhibition of the HOXA9/PBX interaction retards the growth of human meningioma

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Abstract

Background

Meningiomas are the most common type of intracranial tumor, accounting for between 24 and 30 % of primary intracranial tumors. Thus far, no biomarkers exist to reliably predict the clinical outcome of meningiomas. A previous genome-wide methylation analysis revealed that HOXA9 is one of the most functionally relevant biomarkers. In this study, we have examined whether HOXA9 is a potential therapeutic target in meningiomas, using HXR9, a peptide inhibitor of the interaction between HOXA9 and its cofactor PBX.

Methods

We determined the expression level of HOXA9 in human meningiomas, meningioma cell lines, and normal brain tissue. Meningioma in culture and in subcutaneous tumors was treated with HXR9. We also examined the disruption of HOXA9/PBX dimers.

Results

We first confirmed that HOXA9 is highly expressed in meningiomas, but not in normal brain tissue. The HXR9 peptide blocks the binding of HOXA9 to PBX, leading to an alteration of DNA binding, and subsequent regulation of their target genes. HXR9 markedly inhibited the growth of meningioma cells and subcutaneous meningeal tumors.

Conclusion

There is no effective chemotherapy for meningiomas at present, and targeting the HOXA9/PBX interaction may represent a novel treatment option for this disease.

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Acknowledgments

This work was supported by a Grant-in-Aid (B) for Scientific Research from the Japan Society for the Promotion of Science (AN).

Conflict of interest

The authors declare that no conflicts of interest exist.

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Authors and Affiliations

  1. Department of Neurosurgery, Graduate School of Medicine, Nagoya University, 65, Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Hitoshi Ando, Atsushi Natsume, Masasuke Ohno, Kenichiro Iwami, Fumiharu Ohka, Kazuya Motomura, Sayano Kinjo, Maki Ito & Toshishiko Wakabayashi

  2. Department of Cancer Biology, Nagoya University School of Medicine, Nagoya, Japan

    Takeshi Senga

  3. Division of Diagnostic Pathology, Shizuoka Cancer Center, Shizuoka, Japan

    Reiko Watanabe & Ichiro Ito

  4. Department of Neurosurgery, Fukushima Medical University, Fukushima, Japan

    Kiyoshi Saito

  5. Faculty of Health and Medical Sciences, University of Surrey, PGMS 30 PGM 02, Leggett Building, Daphne Jackson Road, Guildford, GU2 7WG, UK

    Richard Morgan

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  1. Hitoshi Ando
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  2. Atsushi Natsume
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Corresponding authors

Correspondence to Atsushi Natsume or Richard Morgan.

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Ando, H., Natsume, A., Senga, T. et al. Peptide-based inhibition of the HOXA9/PBX interaction retards the growth of human meningioma. Cancer Chemother Pharmacol 73, 53–60 (2014). https://doi.org/10.1007/s00280-013-2316-5

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  • DOI: https://doi.org/10.1007/s00280-013-2316-5

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