Association of tumour-associated macrophages with cancer cell EMT, invasion, and metastasis of Kazakh oesophageal squamous cell cancer

Jihong Liu,Lan Yang,Feng Li,Liyan Zhang,Weihua Liang,Jianming Hu,Chunxiao Li,Xueli Wang,Kunping Liu,Kai Liu,Xianli Jiang

doi:10.1186/s13000-019-0834-0

Abstract

BackgroundTumour-associated macrophages (TAMs) play an important role in the growth, progression, and metastasis of tumours. Epithelial-mesenchymal transition (EMT) is a mechanism for tumour invasion and metastasis. In this study, we aimed to determine whether TAMs can induce EMT for the invasion and metastasis of Kazakh oesophageal squamous cell cancer (ESCC).MethodsCD163 was used as a marker for TAMs, and the density of TAMs in tumour nest and surrounding stroma was quantified using immunohistochemistry (IHC). IHC staining was used to evaluate the expression of E-cadherin (epithelial marker) and vimentin (mesenchymal marker) in Kazakh ESCC and cancer-adjacent normal tissues (CANs). Additionally, 6-well transwell plates (0.4 μm) were used to establish the co-culture system of ESCC (EC109 or EC9706) cells and macrophages. Real-time quantitative polymerase chain reaction (qPCR) and western blot experiments were used to determine whether ESCC cells undergo EMT transformation after co-culture with macrophages. Transwell assays were used to detect the migration and invasion of the ESCC cells.ResultsThe distribution of CD163-positive TAMs in cancer tissues was closely related to EMT in Kazakh ESCC. The expression of vimentin in the ESCC cells was significantly upregulated, the expression of E-cadherin was significantly downregulated, and the invasion and migration of the ESCC cells were significantly enhanced after tumour-associated macrophages were added to the co-culture.ConclusionsTumour-associated macrophages promote EMT in ESCC, which may be one of the important factors involved in the invasion and progression of Kazakh ESCC.

Highlights

Tumour-associated macrophages (TAMs) play an important role in the growth, progression, and metastasis of tumours
The TAMs mainly localized in the stroma of cancerous tissues, and a few localized in the cancerous nest (Fig. 1)
Despite no significant correlations with sex and age, we observed a significant negative correlation between E-cadherin expression and tumour differentiation, clinical stage, depth of invasion, lymph node metastasis, and vascular invasion (p < 0.05), we found that the expression of E-cadherin was negatively correlated with tumour differentiation, especially between moderate differentiation and poor differentiation (p < 0.0125)

Summary

Introduction

Tumour-associated macrophages (TAMs) play an important role in the growth, progression, and metastasis of tumours. Epithelial-mesenchymal transition (EMT) is a mechanism for tumour invasion and metastasis. We aimed to determine whether TAMs can induce EMT for the invasion and metastasis of Kazakh oesophageal squamous cell cancer (ESCC). The incidence and mortality rates of Kazakh EC in northwest Xinjiang are higher than the average levels in China [2]. There is growing evidence that the tumour microenvironment is important for tumour progression and metastasis [3,4,5]. Macrophages are important mesenchymal cells in the tumour microenvironment that play an important role in promoting tumour progression, angiogenesis, and metastasis [6]. Macrophages possess plasticity and are classified into different subtypes in different environments, namely, M1 classically activated macrophages, and M2 alternatively activated macrophages [6].

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