The NADPH Oxidase Nox4 mediates tumour angiogenesis.
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| Title: | The NADPH Oxidase Nox4 mediates tumour angiogenesis. |
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| Authors: | Helfinger, V., Henke, N., Harenkamp, S., Walter, M., Epah, J., Penski, C., Mittelbronn, M., Schröder, K. |
| Source: | Acta Physiologica. Apr2016, Vol. 216 Issue 4, p435-446. 12p. 3 Color Photographs, 1 Black and White Photograph, 1 Chart, 2 Graphs. |
| Subjects: | NADPH oxidase, Neovascularization, Tumors, Carcinogens research, Fibrosarcoma |
| Abstract: | 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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| Database: | Psychology and Behavioral Sciences Collection |
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| Abstract: | 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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| ISSN: | 17481708 |
| DOI: | 10.1111/apha.12625 |
