CCL18 in the Progression of Cancer

Int J Mol Sci. 2020 Oct 26;21(21):7955. doi: 10.3390/ijms21217955.

Abstract

A neoplastic tumor consists of cancer cells that interact with each other and non-cancerous cells that support the development of the cancer. One such cell are tumor-associated macrophages (TAMs). These cells secrete many chemokines into the tumor microenvironment, including especially a large amount of CCL18. This chemokine is a marker of the M2 macrophage subset; this is the reason why an increase in the production of CCL18 is associated with the immunosuppressive nature of the tumor microenvironment and an important element of cancer immune evasion. Consequently, elevated levels of CCL18 in the serum and the tumor are connected with a worse prognosis for the patient. This paper shows the importance of CCL18 in neoplastic processes. It includes a description of the signal transduction from PITPNM3 in CCL18-dependent migration, invasion, and epithelial-to-mesenchymal transition (EMT) cancer cells. The importance of CCL18 in angiogenesis has also been described. The paper also describes the effect of CCL18 on the recruitment to the cancer niche and the functioning of cells such as TAMs, regulatory T cells (Treg), cancer-associated fibroblasts (CAFs) and tumor-associated dendritic cells (TADCs). The last part of the paper describes the possibility of using CCL18 as a therapeutic target during anti-cancer therapy.

Keywords: CCL18; PITPNM3; cancer; chemokine; metastasis; regulatory T cells; tumor; tumor-associated macrophages.

Publication types

  • Review

MeSH terms

  • Calcium-Binding Proteins / metabolism
  • Cancer-Associated Fibroblasts / metabolism
  • Chemokines, CC / blood*
  • Chemokines, CC / metabolism*
  • Disease Progression
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Macrophages / metabolism
  • Membrane Proteins / metabolism
  • Neoplasms / blood
  • Neoplasms / metabolism*
  • Prognosis
  • Tumor Escape
  • Tumor Microenvironment
  • Up-Regulation*

Substances

  • CCL18 protein, human
  • Calcium-Binding Proteins
  • Chemokines, CC
  • Membrane Proteins
  • PITPNM3 protein, human