C-C motif chemokine ligand 14 inhibited colon cancer cell proliferation and invasion through suppressing M2 polarization of tumor-associated macrophages

Histol Histopathol. 2021 Jul;36(7):743-752. doi: 10.14670/HH-18-348. Epub 2021 Jun 7.

Abstract

Background: Colon cancer is one of the most common cancers with a high incidence and high mortality. Chemokines play a crucial role in the development of cancer.

Methods: Here, qRT-PCR was performed to detect gene expression. Western blot and immunohistochemistry were implemented to examine the expression of C-C motif chemokine ligand 14 (CCL14) in colon tumors. Besides, the expression of CD68 and CD206 in tumors was measured by immunohistochemistry. The percentages of M1- and M2-polarized macrophages were detected by flow cytometry. Furthermore, CCK-8 assay was performed to detect cell proliferation, and Transwell assay for cell invasion.

Results: CCL14 was decreased in both colon tumors and colon cancer cells, and many tumor-associated macrophages (TAMs) infiltrated into the tumor. An increase CCL14 inhibited colon cancer cell proliferation. Importantly, CCL14 promoted THP-1 to M1 polarization induced by LPS and IFN-γ, and inhibited THP-1 to M2 polarization induced by IL-4 and IL-13. Besides, CCL14 enhanced the inhibition of M1-polarized macrophages to colon cancer cell proliferation and invasion, and reversed the promotion of M2-polarized macrophages to cell proliferation and invasion.

Conclusion: Our data demonstrated that CCL14 inhibited the proliferation and invasion of colon cancer cells through suppressing the formation of M2-like TAMs.

MeSH terms

  • Cell Proliferation / physiology
  • Chemokines, CC / metabolism*
  • Colonic Neoplasms / pathology*
  • Humans
  • Macrophage Activation / physiology
  • Neoplasm Invasiveness / pathology*
  • Tumor-Associated Macrophages / metabolism*
  • Tumor-Associated Macrophages / pathology*

Substances

  • CCL14 protein, human
  • Chemokines, CC