Response gene to complement 32 expression in macrophages augments paracrine stimulation-mediated colon cancer progression

Cell Death Dis. 2019 Oct 10;10(10):776. doi: 10.1038/s41419-019-2006-2.

Abstract

M2-polarized tumor associated macrophages (TAMs) play an important role in tumor progression. It has been reported that response gene to complement 32 (RGC-32) promotes M2 macrophage polarization. However, whether RGC-32 expression in macrophages could play a potential role in tumor progression remain unclear. Here we identified that increasing RGC-32 expression in colon cancer and tumor associated macrophages was positively correlated with cancer progression. In vitro studies confirmed that colon cancer cells upregulated RGC-32 expression of macrophages via secreting TGF-β1. RGC-32 expression promoted macrophage migration. In addition, stimulation of HCT-116 cells with the condition mediums of RGC-32-silienced or over-expressed macrophages affected tumor cell colony formation and migration via altered COX-2 expression. In an animal model, macrophages with RGC-32 knockdown significantly decreased the expression of COX-2 and Ki67 in the xenografts, and partly inhibited tumor growth. Together, our results provide the evidences for a critical role of TGF-β1/RGC-32 pathway in TAMs and colon cancer cells during tumor progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / mortality
  • Colonic Neoplasms / pathology*
  • Cyclooxygenase 2 / metabolism
  • Disease Progression
  • Female
  • Humans
  • Ki-67 Antigen / metabolism
  • Macrophage Activation / drug effects
  • Macrophage Activation / genetics*
  • Macrophages / drug effects
  • Macrophages / enzymology
  • Macrophages / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Paracrine Communication
  • Prognosis
  • Transforming Growth Factor beta1 / metabolism
  • Transforming Growth Factor beta1 / pharmacology
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics*

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • Cell Cycle Proteins
  • Ki-67 Antigen
  • MKI67 protein, human
  • Muscle Proteins
  • Nerve Tissue Proteins
  • RGCC protein, human
  • Transforming Growth Factor beta1
  • Cyclooxygenase 2