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

Peng Zhao,Zhen Zhang,Wei Zhang,Yan Liu,Bing Wang

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.

Highlights

Colorectal cancer (CRC) is the most commonly diagnosed malignancy and the third leading cause of cancer-related death worldwide[1,2]
Our results showed that COX-2 expression was increased in HCT116 cells exposed to the Condition mediums (CMs) of macrophages with RGC32 over-expression and reduced in HCT-116 cells stimulated by the CM of response gene to complement 32 (RGC-32)-silenced macrophage (Fig. 6a)
Macrophages are recruited into the tumor microenvironment and interact with colon cancer cells to facilitate tumor growth and metastasis

Summary

Introduction

Colorectal cancer (CRC) is the most commonly diagnosed malignancy and the third leading cause of cancer-related death worldwide[1,2]. Tumor associated macrophages (TAMs) are the major inflammatory cellular population in tumor microenvironment[5,6]. High frequencies of TAMs were found in tumor tissues of colon cancer patients[7,8]. Some clinical studies imply an important functional contribution of TAMs to poor prognosis or recurrence of colon cancer[9,10]. It is commonly accepted that TAMs are a distinct M2-polarized population promoting tumor progression, including the promotion of tumor cell proliferation, migration and angiogenesis[11,12]. TAMs could be potential targets of therapeutic intervention

Methods

Results

Conclusion