Colon cancer cells secreted CXCL11 via RBP-Jκ to facilitated tumour-associated macrophage-induced cancer metastasis

J Cell Mol Med. 2021 Nov;25(22):10575-10590. doi: 10.1111/jcmm.16989. Epub 2021 Oct 16.

Abstract

Metastasis is the main cause of colon cancer-related deaths. RBP-Jκ is involved in colon cancer development, but its function in colon cancer metastasis is still unclear. Tumour-associated macrophages are the main cell components in tumour microenvironments. Here, we aimed to determine the function of RBP-Jκ in colon cancer metastasis and its underlying mechanisms for modulating interactions between colon cancer cell and tumour-associated macrophages. Through bioinformation analysis, we found that RBP-Jκ was overexpressed in colon cancer tissues and associated with advanced colon cancer phenotypes, macrophage infiltration and shorter survival overall as confirmed by our patients' data. And our patients' data show that RBP-Jκ expression and tumour-associated macrophages infiltration are associated with colon cancer metastasis and are independent prognostic factors for colon cancer patients. Tumour-associated macrophages induced colon cancer cell migration, invasion and epithelial-mesenchymal transition through secreting TGF-β1. Colon cancer cells with high RBP-Jκ expression induced the expression of TGF-β1 in tumour-associated macrophages by secreting CXCL11. Our research revealed that colon cancer cells secreted CXCL11 via overexpression of RBP-Jκ to enhance the expression of TGF-β1 in tumour-associated macrophages to further promote metastasis of colon cancer cells.

Keywords: CXCL11; RBP-Jκ; TAMs; TGF-β1; colon cancer metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Biomarkers
  • Cell Line, Tumor
  • Cell Plasticity / genetics
  • Chemokine CXCL11 / biosynthesis*
  • Colonic Neoplasms / etiology
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / mortality
  • Colonic Neoplasms / pathology*
  • Disease Management
  • Disease Models, Animal
  • Disease Susceptibility
  • Humans
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein / metabolism*
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Mice
  • Neoplasm Staging
  • Receptors, Cell Surface / metabolism
  • Transforming Growth Factor beta1 / metabolism
  • Tumor Microenvironment
  • Tumor-Associated Macrophages / immunology
  • Tumor-Associated Macrophages / metabolism*
  • Tumor-Associated Macrophages / pathology

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers
  • CD163 antigen
  • CXCL11 protein, human
  • Chemokine CXCL11
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein
  • RBPJ protein, human
  • Receptors, Cell Surface
  • Transforming Growth Factor beta1