Myeloid Cell-Derived Reactive Oxygen Species Induce Epithelial Mutagenesis

Canli, Özge; Nicolas, Adele M.; Gupta, Jalaj; Finkelmeier, Fabian; Goncharova, Olga; Pesic, Marina; Neumann, Tobias; Horst, David; Löwer, Martin; Sahin, Ugur and Greten, Florian R. (2017): Myeloid Cell-Derived Reactive Oxygen Species Induce Epithelial Mutagenesis. In: Cancer Cell, Vol. 32, No. 6: pp. 869-883

Abstract

Increased oxidative stress has been suggested to initiate and promote tumorigenesis by inducing DNA damage and to suppress tumor development by triggering apoptosis and senescence. The contribution of individual cell types in the tumor microenvironment to these contrasting effects remains poorly understood. We provide evidence that during intestinal tumorigenesis, myeloid cell-derived H2O2 triggers genome-wide DNA mutations in intestinal epithelial cells to stimulate invasive growth. Moreover, increased reactive oxygen species (ROS) production in myeloid cells initiates tumor growth in various organs also in the absence of a carcinogen challenge in a paracrine manner. Our data identify an intricate crosstalk between myeloid cell-derived ROS molecules, oxidative DNA damage, and tumor necrosis factor alpha-mediated signaling to orchestrate a tumor-promoting microenvironment causing invasive cancer.

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 1535-6108
• Language: English