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Tumor-associated macrophages promote angiogenesis and lymphangiogenesis of gastric cancer

Authors

  • Hui Wu MD, PhD,

    1. Department of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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  • Jian-Bo Xu MD, PhD,

    1. Department of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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  • Yu-Long He MD, PhD,

    Corresponding author
    1. Department of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
    • Department of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, P. R. China. Fax: +86-20-87331059.
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  • Jian-Jun Peng MD, PhD,

    1. Department of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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  • Xin-Hua Zhang MD, PhD,

    1. Department of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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  • Chuang-Qi CHEN MD, PhD,

    1. Department of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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  • Wen Li PhD,

    1. Department of Surgical Laboratory, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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  • Shi-Rong Cai MD, PhD

    1. Department of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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  • Hui Wu and Jian-Bo Xu contributed equally to this study.

  • Conflict of interest: None.

Abstract

Background and Objectives

This study was conducted to investigate whether and how macrophages recruited to tumor microenvironments (tumor-associated macrophages, TAMs) were involved in angiogenesis and lymphangiogenesis of gastric cancer (GC).

Methods

TAMs, microvessel density (MVD), and lymphatic vessel density (LVD) in 115 cases of GC tissue were assessed by immunohistochemistry (IHC) staining of CD68, CD34, and D2-40, respectively. Preoperative blood samples from 43 patients were obtained to detect serum levels of vascular endothelial growth factor (VEGF) and VEGF-C. A co-culture system was also developed to study effects and underlying mechanisms of THP-1 macrophages on SGC7901 GC cells.

Results

TAMs numbers were closely related to serosa invasion, lymph node metastasis and tumor, nodes, and metastases stage and a positive correlation existed between the TAMs count and MVD and LVD. Additionally, TAMs were associated with preoperative serum levels of VEGF and VEGF-C, the expression of VEGF and VEGF-C protein in macrophages was up-regulated in the co-culture system, and inhibition of the NF-κB pathway in macrophages induced a significant reduction in the expression of VEGF and VEGF-C in both macrophages and GC cells (all P < 0.05).

Conclusions

TAMs may promote angiogenesis and lymphangiogenesis of GC, possibly by enhancing VEGF and VEGF-C expression. J. Surg. Oncol. 2012; 106:462–468. © 2012 Wiley Periodicals, Inc.

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