Infiltration of CD204-overexpressing Macrophages Contributes to the Progression of Stage II and III Colorectal Cancer

Anticancer Res. 2021 Oct;41(10):4857-4865. doi: 10.21873/anticanres.15299.

Abstract

Background/aim: M1 macrophages have antitumour effects, while M2 macrophages promote tumour proliferation and invasion. The clinical significance of the M2-specific marker CD204 has not been elucidated in colorectal cancer (CRC). We investigated the prognostic significance of CD204- and CD68-positivity in specimens from patients with CRC and examined the effects of M2 polarized-macrophages on the proliferative and invasive potentials of CRC cell lines in vitro.

Materials and methods: Surgical tumour specimens from 206 patients with Stage II and III CRC were examined by immunohistochemistry. Proliferation and invasion assays and flow cytometry were used to investigate CD204 expression in macrophages co-cultured with three CRC cell lines.

Results: Infiltration of CD204-positive cells was significantly associated with shorter overall survival and relapse-free survival; no association was observed for CD68. M2-polarized macrophages significantly promoted proliferation and invasion of CRC cells.

Conclusion: Higher infiltration of CD204-positive macrophages into the tumour-microenvironment might be prognostically important in CRC.

Keywords: CD204; CD68; M2 macrophage; colorectal cancer.

MeSH terms

  • Aged
  • Antigens, CD / immunology
  • Antigens, Differentiation, Myelomonocytic / immunology
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Disease-Free Survival
  • Female
  • Humans
  • Macrophage Activation
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Prognosis
  • Scavenger Receptors, Class A / immunology*
  • Survival Rate
  • Tumor Microenvironment / immunology
  • Tumor-Associated Macrophages / immunology*

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • MSR1 protein, human
  • Scavenger Receptors, Class A