Effects of tumor-associated macrophages on the proliferation and migration of esophageal cancer-associated lymphatic endothelial cells

J Biol Regul Homeost Agents. 2018 Mar-Apr;32(2):207-218.

Abstract

The aim of this study was to explore whether M2 macrophages can be transformed into M1 macrophages, and to investigate the effect of different types of macrophages on the proliferation, migration and ring-forming ability of esophageal cancer-related lymphatic endothelial cell (LEC). Human monocytic leukemia cell line (THP-1 cell) was induced to differentiate to M1 macrophages (M1 group) and M2 macrophages (M2 group), and co-cultured with esophageal cancer-associated LEC. The individual esophageal cancer co-cultured with LEC was used as control. Different types of macrophages were observed by Cell counting kit-8 (CCK-8). Enzyme-linked immunosorbent assay (ELISA) was used to detect the VEGF-C concentration; the expression of VEGFR-3 protein and its mRNA was detected by Western blot and qRT-PCR, respectively. The positive rate of the M1 group induced by IFN-γ and LPS was significantly higher than that of M2 macrophages (48.57%5.98% vs 25.83%1.95%). The expression of VEGF-C in the supernatant of the M2 group was higher than that in the control group, but no significant differences regarding the expression of VEGF-C between M1 and control groups were found. In addition, the expression of VEGFR-3 on both mRNA and protein in esophageal cancer-related LEC of the M2 group was significantly higher than those in the control group; however, the M1 group had a significantly lower VEGFR-3 level on both mRNA and protein than the control group. Human M2 macrophages can be transformed into M1 macrophages, and can promote the proliferation, migration and ring-forming ability of esophageal cancer-associated LEC.

MeSH terms

  • Cell Differentiation / physiology
  • Cell Line
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Coculture Techniques
  • Endothelial Cells / pathology*
  • Esophageal Neoplasms / pathology*
  • Humans
  • Lymphangiogenesis / physiology*
  • Macrophages / metabolism*
  • Macrophages / pathology