title: Mice lacking NCF1 exhibit reduced growth of implanted melanoma and carcinoma tumors.
abstract: The NADPH oxidase 2 (NOX2) complex is a professional producer of reactive oxygen species (ROS) and is mainly expressed in phagocytes. While the activity of the NOX2 complex is essential for immunity against pathogens and protection against autoimmunity, its role in the development of malignant tumors remains unclear. We compared wild type and Ncf1 (m1J) mutated mice, which lack functional NOX2 complex, in four different tumor models. Ncf1 (m1J) mutated mice developed significantly smaller tumors in two melanoma models in which B16 melanoma cells expressing a hematopoietic growth factor FLT3L or luciferase reporter were used. Ncf1 (m1J) mutated mice developed significantly fewer Lewis Lung Carcinoma (LLC) tumors, but the tumors that did develop, grew at a pace that was similar to the wild type mice. In the spontaneously arising prostate carcinoma model (TRAMP), tumor growth was not affected. The lack of ROS-mediated protection against tumor growth was associated with increased production of immunity-associated cytokines. A significant increase in Th2 associated cytokines was observed in the LLC model. Our present data show that ROS regulate rejection of the antigenic B16-luc and LLC tumors, whereas the data do not support a role for ROS in growth of intrinsically generated tumors.
authors.affiliation: Medicity Research Laboratory, Turku, Finland ; Turku Doctoral Programme of Biomedical Sciences, Turku, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Kelkka
authors.affiliation: Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Angela
authors.initials: A
authors.lastname: Pizzolla
authors.affiliation: Medicity Research Laboratory, Turku, Finland.
authors.forename: Juha Petteri
authors.initials: JP
authors.lastname: Laurila
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala.
authors.forename: Tomas
authors.initials: T
authors.lastname: Friman
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala.
authors.forename: Renata
authors.initials: R
authors.lastname: Gustafsson
authors.affiliation: Immunology Group, Biomedical Center, Lund University, Lund, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Källberg
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala.
authors.forename: Olof
authors.initials: O
authors.lastname: Olsson
authors.affiliation: Immunology Group, Biomedical Center, Lund University, Lund, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Leanderson
authors.affiliation: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala.
authors.forename: Kristofer
authors.initials: K
authors.lastname: Rubin
authors.affiliation: Medicity Research Laboratory, Turku, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Salmi
authors.affiliation: Medicity Research Laboratory, Turku, Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Jalkanen
authors.affiliation: Medicity Research Laboratory, Turku, Finland ; Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018827:Carcinoma, Lewis Lung; D004195:Disease Models, Animal; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008546:Melanoma, Experimental; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000276:immunology; D047368:Tumor Burden / Q000235:genetics
chemical_list: D008565:Membrane Proteins; D017382:Reactive Oxygen Species; C084881:flt3 ligand protein; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1