Increased IL-10 mRNA expression in tumor-associated macrophage correlated with late stage of lung cancer

Rui Wang,Xiaoyang Luo,Ying Qin,Sufeng Chen,Meng Lu,Haiquan Chen,Jie Zhang

doi:10.1186/1756-9966-30-62

Abstract

BackgroundMonocyte recruited into the tumor and maturation to tumor-associated macrophage (TAM). Interleukin-10(IL-10) is a potent immunosuppressive cytokine, which can be secreted from both primary tumor and stromal cells. However, there are controversies regarding its role in the progression of cancer. So it is important to isolate TAM from tumor cells to study the role of IL-10 in the progress of cancer. The aim of our study was to determine whether IL-10 expressed by TAM correlated with clinicopathological factors in NSCLC.MethodsTAM in NSCLC was isolated by short-term culture in serum free medium with the modification to literature reports. The mRNA expression levels of IL-10, cathepsin B, cathepsin S, which were closely related with TAM according to the literatures, were evaluated by Quantitative real-time RT-PCR in 63 NSCLC. The relationships between their expression levels and clinicopathological features were investigated.ResultsWe successfully achieved up to 95% purity of TAM, derived from 63 primary lung cancer tissues. TAM expressed high levels of IL-10, cathepsin B in NSCLC. High levels of IL-10 in TAM significantly correlated with stage, tumor size, lymph node metastasis, lymphovascular invasion or histologic poor differentiation.ConclusionsOur results revealed that TAM with high levels of IL-10 expression may play an important role in the progression of non-small cell lung cancer. The data also suggested that TAMs may involve in tumor immunosuppression through overexpressed IL-10. Additionally, the phenotype of isolated TAM can be potentially used to predict clinicopathological features as well.

Highlights

Monocyte recruited into the tumor and maturation to tumor-associated macrophage (TAM)
Recent animal model studies indicated that cathepsin B or cathepsin S expressed by TAM play an important role in tumor progression [10,11], and we found cathepsin B upregulated in TAM, we failed to demonstrate any correlation between cathepsin B in TAM and stage, lymph nodal metastasis, pleural invasion or differentiation in NSCLC
Our studies demonstrated that TAM isolated from NSCLC overexpressed cathepsin B but not cathepsin S, and the cathepsin B levels were not associated with NSCLC stage, lymph metastasis, lymphovascular invasion or histological differentiation

Summary

Introduction

Monocyte recruited into the tumor and maturation to tumor-associated macrophage (TAM). It is important to isolate TAM from tumor cells to study the role of IL-10 in the progress of cancer. Tumor-associated macrophages (TAMs) are the most abundant cancer stromal cells involved in the host immune system [1,2]. In recent years, increasing attention has focused on TAMs, unique macrophage populations that play pivotal roles in tumor immunosuppression, and provide a suitable microenvironment for cancer development and progression[3]. Interleukin-10(IL-10), cathepsin B or cathepsin S was reported to be closely associated with TAMs in recent literatures [10,11,12]. Previous reports have shown that TAMs produce high levels of IL-10, exhibit little cytotoxicity for tumor cells[14]. There are controversies regarding its role in the progression of cancer [15,16]

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