Colorectal cancer cell-derived interleukin-6 enhances the phagocytic capacity and migration of THP-1 cells

Cytokine. 2016 Mar:79:82-9. doi: 10.1016/j.cyto.2016.01.001. Epub 2016 Jan 8.

Abstract

Macrophages perform a versatile range of functions in response to environmental stimuli. In the present study, we evaluated whether interleukin-6 (IL-6), a cytokine released from colorectal cancer (CRC) cells and associated with CRC pathogenesis and metastasis, modulates the phagocytic capacity and migratory ability of macrophages, using a monocyte-macrophage THP-1 cell model and human peripheral monocytes. We found that CRC cells enhanced the phagocytic capacity and migration of THP-1 cells and human peripheral monocytes. CRC cell culture supernatants and recombinant IL-6 neutralized with anti-IL-6 and anti-gp130 antibodies considerably decreased IL-6-mediated phagocytosis by and migration of THP-1 cells and human peripheral monocytes, via the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Our data suggest that CRC cells secreting IL-6 via STAT3 phosphorylation can enhance the phagocytic capacity and migration of macrophages in the tumor microenvironment.

Keywords: Colorectal cancer; Interleukin-6; Macrophages; Migration; Phagocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / immunology
  • Cell Line, Tumor
  • Cell Movement / immunology*
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / pathology
  • Culture Media, Conditioned / pharmacology
  • Cytokine Receptor gp130 / immunology
  • Enzyme Activation / immunology
  • HT29 Cells
  • Humans
  • Interleukin-6 / immunology*
  • Interleukin-6 / pharmacology
  • Macrophages / immunology*
  • Monocytes / immunology*
  • Phagocytosis / immunology*
  • Phosphorylation
  • Recombinant Proteins / pharmacology
  • STAT3 Transcription Factor / metabolism*
  • Tumor Microenvironment / immunology

Substances

  • Antibodies
  • Culture Media, Conditioned
  • IL6 protein, human
  • Interleukin-6
  • Recombinant Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Cytokine Receptor gp130