Functions of tumor-associated macrophages and macrophages residing in remote anatomical niches in Ehrlich carcinoma bearing mice

Exp Oncol. 2020 Sep;42(3):197-203. doi: 10.32471/exp-oncology.2312-8852.vol-42-no-3.14928.

Abstract

Background: The impact of growing tumor on polarization and functions of tumor-associated macrophages is well known while its influence on residential macrophages occupying different anatomical niches reminds to be elucidated.

Aim: To study changes in polarization and functions of macrophages isolated from discrete anatomical niches in tumor-bearing mice at different stages of tumor growth.

Materials and methods: Ehrlich carcinoma was transplanted intramuscularly to Balb/c male mice. On days 7, 14, 21 and 28 after tumor transplantation, macrophages from tumor tissue, peritoneal cavity and spleen were isolated and analyzed. Nitric oxide production was measured by standard Griess reaction, arginase activity was determined by the measurement of urea, reactive oxygen species production was checked using NBT dye reduction assay and electron paramagnetic resonance spectroscopy, cytotoxic activity was estimated in MTT-assay.

Results: Independently of their localization in different anatomic niches, macrophages in mice with transplanted Ehrlich carcinoma gradually lose their tumoricidal activities while arginase activity is upregulated. This indicates the shift of polarization from M1-like towards M2-like phenotype.

Conclusion: Our findings demonstrated that growing tumor could be able to subvert functioning of macrophages at the systemic level.

MeSH terms

  • Animals
  • Arginase / metabolism
  • Carcinoma, Ehrlich Tumor / immunology*
  • Carcinoma, Ehrlich Tumor / metabolism
  • Carcinoma, Ehrlich Tumor / pathology*
  • Cytotoxicity, Immunologic
  • Macrophage Activation / genetics
  • Macrophage Activation / immunology
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide / metabolism
  • Organ Specificity / immunology
  • Oxidation-Reduction
  • Reactive Oxygen Species / metabolism
  • Tumor Burden
  • Tumor Microenvironment / immunology*
  • Tumor-Associated Macrophages / immunology*
  • Tumor-Associated Macrophages / metabolism
  • Tumor-Associated Macrophages / pathology

Substances

  • Reactive Oxygen Species
  • Nitric Oxide
  • Arginase