Mice lacking NCF1 exhibit reduced growth of implanted melanoma and carcinoma tumors

• Published in: PloS one Vol. 8; no. 12; p. e84148
• Main Authors: Kelkka, Tiina, Pizzolla, Angela, Laurila, Juha Petteri, Friman, Tomas, Gustafsson, Renata, Källberg, Eva, Olsson, Olof, Leanderson, Tomas, Rubin, Kristofer, Salmi, Marko, Jalkanen, Sirpa, Holmdahl, Rikard
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.12.2013; Public Library of Science (PLoS)
• Subjects: Animal models; Animals; Antigens; Autoimmunity; B cells; Basic Medicine; Biochemistry; Biophysics; Cancer; Carcinoma; Carcinoma - genetics; Carcinoma - metabolism; Carcinoma - mortality; Carcinoma - pathology; Carcinoma, Lewis Lung; Cell growth; Comparative analysis; CYBB protein; Cytokines; Disease Models, Animal; Experiments; FLT3L protein; Gene expression; Growth; Hematology; Immunity; Immunologi inom det medicinska området; Immunology; Immunology in the medical area; Inflammation; Inflammation - genetics; Inflammation - metabolism; Laboratories; Leukemia; Lung cancer; Lung carcinoma; Lymphocytes; Lymphocytes T; Medical and Health Sciences; Medical research; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Melanoma; Melanoma - genetics; Melanoma - metabolism; Melanoma - mortality; Melanoma - pathology; Melanoma, Experimental; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mutation; NAD(P)H oxidase; NADPH Oxidases - deficiency; NADPH Oxidases - genetics; NADPH Oxidases - metabolism; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - mortality; Neoplasms - pathology; Oxidases; Oxygen; Phagocytes; Prostate; Prostate cancer; Prostate carcinoma; Reactive oxygen species; Reactive Oxygen Species - immunology; Rheumatoid arthritis; Tumor Burden - genetics; Tumors; Sweden; Santa Barbara California; California; United States > US; Finland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0084148

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.