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Oncol Rep. 2017 Oct;38(4):2003-2010. doi: 10.3892/or.2017.5877. Epub 2017 Aug 3.

Tumor-associated macrophages induce the expression of FOXQ1 to promote epithelial-mesenchymal transition and metastasis in gastric cancer cells.

Author information

1
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
2
The Second Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
3
Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
4
Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
5
Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
6
Departments of Medicine and Physiology, McGill University, Montreal, Quebec H3A 1A1, Canada.

Abstract

Gastric cancer (GC) is one of the most common malignancies, and is the second leading cause of cancer-related deaths worldwide. Macrophages infiltrated in the tumor microenvironment (TME) called tumor-associated macrophages (TAMs) are key orchestrators in TME. In GC, it has been reported that infiltration of TAMs is associated with epithelial-mesenchymal transition (EMT)-related proteins in human GC tissues, but the exactly mechanism has not been clarified. In the present study, we aimed to elucidate the underlying mechanism of TAMs on GC cells. THP-1 cells were used to investigate the effects of TAMs on GC cells. The effects of invasion and migration induced by coculture with TAMs were investigated by Transwell invasion and wound healing assays. The expression of EMT-related genes and forkhead box Q1 (FOXQ1) were examined in MKN45 and MKN74 cells after being co-cultured with TAMs. The density of TAMs and the expression of FOXQ1 were analyzed by immunohistochemistry in GC tissues. Our results revealed that, co-culture with TAMs promoted the invasion and migration of GC cells. Co-culture with TAMs induced EMT in GC cells. FOXQ1 is essential for TAM-induced EMT and metastasis in GC cells. Furthermore, silencing of FOXQ1 blocked the effect of TAM-enhanced EMT and metastasis of GC cells. High expression of CD68 was correlated with positive FOXQ1 expression (r=0.613; P<0.001) in clinical GC samples. Our data provided evidence that TAMs promote EMT, invasion and migration of GC cells via FOXQ1. Therefore, the TAM/FOXQ1 axis may represent a novel target for GC cells.

PMID:
28791370
PMCID:
PMC5652949
DOI:
10.3892/or.2017.5877
[Indexed for MEDLINE]
Free PMC Article

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