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01.01.2014 | Original Article

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

verfasst von: Hitoshi Ando, Atsushi Natsume, Takeshi Senga, Reiko Watanabe, Ichiro Ito, Masasuke Ohno, Kenichiro Iwami, Fumiharu Ohka, Kazuya Motomura, Sayano Kinjo, Maki Ito, Kiyoshi Saito, Richard Morgan, Toshishiko Wakabayashi

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 1/2014

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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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Titel: Peptide-based inhibition of the HOXA9/PBX interaction retards the growth of human meningioma
verfasst von: Hitoshi Ando
Atsushi Natsume
Takeshi Senga
Reiko Watanabe
Ichiro Ito
Masasuke Ohno
Kenichiro Iwami
Fumiharu Ohka
Kazuya Motomura
Sayano Kinjo
Maki Ito
Kiyoshi Saito
Richard Morgan
Toshishiko Wakabayashi
Publikationsdatum: 01.01.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 1/2014
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-013-2316-5

Springer Medizin

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