Cancer-associated fibroblasts promote colorectal cancer progression by secreting CLEC3B

Cancer Biol Ther. 2019;20(7):967-978. doi: 10.1080/15384047.2019.1591122. Epub 2019 Mar 20.

Abstract

Nontumour cells in the tumour microenvironment, especially fibroblasts, contribute to tumour progression and metastasis. The occurrence and evolution of colorectal cancer (CRC) is closely related to cancer-associated fibroblasts (CAFs). The aim of this work was to evaluate the effects of the growth factors and cytokines secreted by CAFs on CRC progression. The secreted cytokines were examined in CAFs by Human Cytokine Antibody array. We screened 37 differentially secreted cytokines in the culture supernatants of CAFs and NFs. CLEC3B, attractin, kallikrein 5 and legumain were selected for further verification. CLEC3B was more highly expressed in the stroma of CRC tissues than the other 3 cytokines. Immunohistochemistry revealed that CLEC3B expression was associated with serosal invasion by CRC. Patients with co-expression of CLEC3B and α-SMA had worse survival outcomes than those with only CLEC3B or α-SMA expression. CLEC3B secreted from CAFs may promote tumour migration. Knockdown of endogenous CLEC3B in CAFs markedly decreased CRC cell migration, while recombinant human CLEC3B clearly promoted CRC cell migration and actin remodelling. In conclusion, our findings suggest that CAFs promote the CRC cell migration and skeletal reorganization by secreting CLEC3B. CLEC3B might be a potential therapeutic molecule for CRC treatment.

Keywords: CLEC3B; Cancer-associated fibroblasts (CAFs); colorectal cancer (CRC); migration; α-SMA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Adult
  • Aged
  • Biomarkers
  • Cancer-Associated Fibroblasts / metabolism*
  • Cancer-Associated Fibroblasts / pathology*
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology*
  • Disease Progression
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunohistochemistry
  • Lectins, C-Type / biosynthesis*
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Tumor Microenvironment / genetics

Substances

  • Actins
  • Biomarkers
  • Lectins, C-Type
  • tetranectin

Grants and funding

This work was supported by grants from The National Natural Science Foundation of China(NNSF81201664, NNSF81672437), The Provincial Science Foundation of Guangdong (2014A030313304) and The Science Foundation of Guangdong Second Provincial General Hospital(YQ2015-003).