Home > Publikationen > 2017 > 29232557

Myeloid Cell-Derived Reactive Oxygen Species Induce Epithelial Mutagenesis.

Canli Ö, Nicolas AM, Gupta J, Finkelmeier F, Goncharova O, Pesic M, Neumann T, Horst D, Löwer M, Sahin U, Greten FR
Cancer cell 2017; 3262017Dec11: 869-883.e5

Zusammenfassung

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 H2O2triggers 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 α-mediated signaling to orchestrate a tumor-promoting microenvironment causing invasive cancer.

Zugehörigkeit: Institute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, 60596 Frankfurt/Main, Germany.

Aritkel auf PubMed

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