The Preventive Effect of the Phenotype of Tumour-Associated Macrophages, Regulated by CD39, on Colon Cancer in Mice

Int J Mol Sci. 2021 Jul 13;22(14):7478. doi: 10.3390/ijms22147478.

Abstract

Background: This study was designed to investigate the effect of cluster differentiation (CD)39 and CD73 inhibitors on the expresion of tumour-associated macrophages (TAMs), M1- versus M2-tumour phenotypes in mice with colon cancer.

Methods: An in vivo study of co-culture with colon cancer cells and immune cells from the bone marrow (BM) of mice was performed. After the confirmation of the effect of polyoxotungstate (POM-1) as an inhibitor of CD39 on TAMs, the mice were randomly divided into a control group without POM-1 and a study group with POM-1, respectively, after subcutaneous injection of CT26 cells. On day 14 after the injection, the mice were sacrificed, and TAMs were evaluated using fluorescence-activated cell sorting.

Results: In the in vivo study, the co-culture with POM-1 significantly increased the apoptosis of CT26 cells. The cell population from the co-culture with POM-1 showed significant increases in the expression of CD11b+ for myeloid cells, lymphocyte antigen 6 complex, locus C (Ly6C+) for monocytes, M1-tumour phenotypes from TAMs, and F4/80+ for macrophages. In the in vivo study, tumour growth in the study group with POM-1 was significantly limited, compared with the control group without POM-1. The expressions of Ly6C+ and major histocompatibility complex class II+ for M1-tumour phenotypes from TAMs on F4/80+ from the tumour tissue in the study group had significantly higher values compared with the control group.

Conclusion: The inhibition of CD39 with POM-1 prevented the growth of colon cancer in mice, and it was associated with the increased expression of M1-tumour phenotypes from TAMs in the cancer tissue.

Keywords: CD39; CD73; colon cancer; tumour-associated macrophage.

MeSH terms

  • Animals
  • Antigens, CD
  • Apoptosis
  • Apyrase / antagonists & inhibitors*
  • Cell Proliferation
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / prevention & control*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Polymers / pharmacology*
  • Prognosis
  • Tumor Cells, Cultured
  • Tumor-Associated Macrophages / drug effects*
  • Tumor-Associated Macrophages / metabolism
  • Tumor-Associated Macrophages / pathology
  • Tungsten Compounds / pharmacology*
  • Xenograft Model Antitumor Assays

Substances

  • Antigens, CD
  • Polymers
  • Tungsten Compounds
  • polyoxotungstate PM 19
  • Apyrase
  • CD39 antigen