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The NADPH Oxidase Nox4 mediates tumour angiogenesis.
In: Acta Physiologica, Jg. 216 (2016-04-01), Heft 4, S. 435-446
Online
academicJournal
Zugriff:
Aim The aim of this work was to identify the role of the NADPH oxidase Nox4 for tumour angiogenesis in a slow-growing tumour model in mice. Methods Tumour angiogenesis was studied in tumours induced by the carcinogen 3-methylcholanthrene ( MCA) in wild-type and Nox knockout mice. Mice were killed when the tumour reached a diameter of 1.5 cm and tumour tissue was used for histological and molecular analysis. Results 3-methylcholanthrene induced fibrosarcoma in wild-type, Nox1y/-, Nox2y/- and Nox4-/- mice. Histological analysis of vessel density using anti- CD31 staining showed a significant 38% reduction in tumour vascularization in fibrosarcomas of Nox4-/- mice. In contrast, tumour angiogenesis was doubled in Nox1 knockout mice, whereas knockout of Nox2 had no effect on tumour-vessel density. As underlying mechanisms, we identified a defect in hypoxia signalling in Nox4-/- mice. Hypoxia-inducible factor 1-alpha (Hif-1 α) accumulation in the tumours was attenuated as was the expression of the Hif-1 α-dependent pro-angiogenic genes vascular endothelial growth factor -A, glucose transporter 1 and adrenomedullin. Conclusion By regulating the tumour-vessel density through stabilization of Hif-1 α and induction of VEGF expression, Nox4 promotes tumour angiogenesis and may represent a novel target for anti-angiogenic tumour therapy. [ABSTRACT FROM AUTHOR]
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The NADPH Oxidase Nox4 mediates tumour angiogenesis.
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Autor/in / Beteiligte Person: | Helfinger, V. ; Henke, N. ; Harenkamp, S. ; Walter, M. ; Epah, J. ; Penski, C. ; Mittelbronn, M. ; Schröder, K. |
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Zeitschrift: | Acta Physiologica, Jg. 216 (2016-04-01), Heft 4, S. 435-446 |
Veröffentlichung: | 2016 |
Medientyp: | academicJournal |
ISSN: | 1748-1708 (print) |
DOI: | 10.1111/apha.12625 |
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