Tumor angiogenesis is caused by single melanoma cells in a manner dependent on reactive oxygen species and NF-κb

Schaafhausen MK, Yang WJ, Centanin L, Wittbrodt J, Bosserhoff A, Fischer A, Schartl M, Meierjohann S (2013)

Publication Type: Journal article

Publication year: 2013

Journal

Journal of cell science

Book Volume: 126

Pages Range: 3862-3872

Journal Issue: 17

DOI: 10.1242/jcs.125021

Abstract

Melanomas have a high angiogenic potential, but respond poorly to medical treatment and metastasize very early. To understand the early events in tumor angiogenesis, animal models with high tumor resolution and blood vessel resolution are required, which provide the opportunity to test the ability of small molecule inhibitors to modulate the angiogenic tumor program. We have established a transgenic melanoma angiogenesis model in the small laboratory fish species Japanese medaka. Here, pigment cells are transformed by an oncogenic receptor tyrosine kinase in fish expressing GFP throughout their vasculature. We show that angiogenesis occurs in a reactive oxygen species (ROS)- and NF-kB-dependent, but hypoxia-independent manner. Intriguingly, we observed that blood vessel sprouting is induced even by single transformed pigment cells. The oncogenic receptor as well as human melanoma cells harboring other oncogenes caused the production of pro-angiogenic factors, most prominently angiogenin, through NF-κB signaling. Inhibiting NF-κB prevented tumor angiogenesis and led to the regression of existing tumor blood vessels. In conclusion, our high-resolution medaka melanoma model discloses that ROS and NF-κB signaling from single tumor cells causes hypoxia-independent angiogenesis, thus, demonstrating that the intrinsic malignant tumor cell features are sufficient to initiate and maintain a pro-angiogenic signaling threshold. © 2013. Published by The Company of Biologists Ltd.

Involved external institutions

Julius-Maximilians-Universität Würzburg DE Germany (DE) DKFZ-ZMBH Alliance, Center for Molecular and Cellular Biology (ZMBH) DE Germany (DE) Ruprecht-Karls-Universität Heidelberg DE Germany (DE) Universität Regensburg DE Germany (DE)

How to cite

APA:

Schaafhausen, M.K., Yang, W.-J., Centanin, L., Wittbrodt, J., Bosserhoff, A., Fischer, A.,... Meierjohann, S. (2013). Tumor angiogenesis is caused by single melanoma cells in a manner dependent on reactive oxygen species and NF-κb. Journal of cell science, 126(17), 3862-3872. https://doi.org/10.1242/jcs.125021

MLA:

Schaafhausen, Maximilian K., et al. "Tumor angiogenesis is caused by single melanoma cells in a manner dependent on reactive oxygen species and NF-κb." Journal of cell science 126.17 (2013): 3862-3872.

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