title: Targeting extracellular ROS signaling of tumor cells.
abstract: Expression of membrane-associated NADPH oxidase (NOX1) represents a characteristic feature of malignant cells. NOX1-derived extracellular superoxide anions are the basis for autocrine stimulation of proliferation, but also drive the HOCl and the NO/peroxynitrite signaling pathways. This may cause the elimination of transformed cells. Tumor cells express membrane-associated catalase that efficiently protects the cells against apoptosis-inducing reactive oxygen species (ROS) signaling. Membrane-associated superoxide dismutase (SOD) plays a co-modulatory protective role that is functionally interrelated with the protective effect mediated by catalase. Due to the co-localization of NOX1, catalase and SOD on the outer membrane of tumor cells, specific inhibition of membrane-associated SOD causes superoxide anion-dependent inhibition of catalase. This establishes a strong apoptotic signaling through the NO/peroxynitrite pathway. In parallel, it causes a drastic decrease in the concentration of proliferation-stimulating H2O2. Knowledge of the biochemical network on the surface of tumor cells should, therefore, allow development of specific novel strategies for tumor therapy, based on the specific features of tumor cell-specific extracellular ROS interactions.
authors.affiliation: Institute of Virology, Department of Medical Microbiology and Hygiene, University of Freiburg, Hermann-Herder Strasse 11, D-79104 Freiburg, Germany. georg.bauer@uniklinik-freiburg.de.
authors.forename: Georg
authors.initials: G
authors.lastname: Bauer
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D002374:Catalase; D013482:Superoxide Dismutase
keywords: NOX1; ROS; apoptosis; catalase; review; superoxide anion; superoxide dismutase