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Inhibitor of DNA binding-4 promotes angiogenesis and growth of glioblastoma multiforme by elevating matrix GLA levels

Oncogene volume 29, pages 3793–3802 (2010)Cite this article

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Abstract

Inhibitor of differentiation-4 is highly expressed in glioblastoma multiforme (GBM). We report a novel pro-angiogenic function for inhibitor of differentiation-4 in the growth of glioblastoma xenografts. Tumor-derived cell cultures expressing elevated levels of ID4 produced enlarged xenografts in immunosuppressed mice that were better vascularized than corresponding control tumors and expressed elevated matrix GLA protein (MGP) that mediated enhanced tumor angiogenesis. Inhibition of MGP resulted in smaller and less vascularized xenografts. Our finding shows a novel function for ID4 in tumor angiogenesis, and identifies ID4 and MGP as possible therapeutic targets for GBM.

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Acknowledgements

Many thanks to Dr Kristina I Boström for lending her expertise, sharing reagents, and fielding generously many questions about MGP. This work was supported by funding from the Theodora B. Betz Foundation (MAI) and the Jordan & Kyra Foundation (MAI).

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  1. P M Kuzontkoski

    Present address: 4Current address: Division of Experimental Medicine and Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA.,

Authors and Affiliations

  1. Departments of Pediatrics and Genetics, Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH, USA

    P M Kuzontkoski & M A Israel

  2. Department of Surgery, Vascular Section, Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH, USA

    M J Mulligan-Kehoe

  3. Department of Pathology, Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, NH, USA

    B T Harris

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Correspondence to M A Israel.

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Kuzontkoski, P., Mulligan-Kehoe, M., Harris, B. et al. Inhibitor of DNA binding-4 promotes angiogenesis and growth of glioblastoma multiforme by elevating matrix GLA levels. Oncogene 29, 3793–3802 (2010). https://doi.org/10.1038/onc.2010.147

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