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

PLoS One. 2013 Dec 16;8(12):e84148. doi: 10.1371/journal.pone.0084148. eCollection 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Carcinoma / mortality
  • Carcinoma / pathology*
  • Carcinoma, Lewis Lung
  • Disease Models, Animal
  • Inflammation / genetics
  • Inflammation / metabolism
  • Melanoma / genetics*
  • Melanoma / metabolism
  • Melanoma / mortality
  • Melanoma / pathology*
  • Melanoma, Experimental
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mutation
  • NADPH Oxidases / deficiency
  • NADPH Oxidases / genetics*
  • NADPH Oxidases / metabolism
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / mortality
  • Neoplasms / pathology*
  • Reactive Oxygen Species / immunology
  • Tumor Burden / genetics

Substances

  • Membrane Proteins
  • Reactive Oxygen Species
  • flt3 ligand protein
  • NADPH Oxidases
  • neutrophil cytosolic factor 1

Grants and funding

This study was supported by grants from the Swedish Strategic Science Foundation, Knut and Alice Wallenberg foundation, Swedish Research Council, Swedish Rheumatism Association, Swedish Cancer Society, The Alfred Östelunds Stiftelse (Sweden), Juselius Foundation, Finnish Academy, the Finnish Cancer Foundation, Svenska Kulturfonden in Finland, EU Masterswitch (Grant No. HEALTH- F2-2008-223404), Neurinox and BeTheCure grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript