Tumor-associated macrophages promote angiogenesis and lymphangiogenesis of gastric cancer
Tumor-associated macrophages promote angiogenesis and lymphangiogenesis of gastric cancer
复制标题
肿瘤相关巨噬细胞促进胃癌的血管生成和淋巴管生成。
DOI：
10.1002/jso.23110
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发表时间：
2012-09-01
影响因子：
2.5
通讯作者：
Cai, Shi-Rong
中科院分区：
文献类型：
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作者：
Wu, Hui;Xu, Jian-Bo;Cai, Shi-Rong
背景与目的本研究旨在探讨肿瘤微环境中募集的巨噬细胞（tumor-associated macrophages，TAMs）是否以及如何参与胃癌（gastric cancer，GC）血管生成和淋巴管生成。方法采用免疫组织化学方法检测115例胃癌组织中TAMs、微血管密度（MVD）和淋巴管密度（LVD）。43例患者术前取血检测血清血管内皮生长因子（VEGF）和VEGF-C水平。建立了THP-1巨噬细胞与胃癌细胞共培养体系，研究了THP-1巨噬细胞对胃癌细胞的作用及其机制。结果TAMs数与浆膜浸润、淋巴结转移、肿瘤分期、淋巴结转移密切相关，与MVD、LVD呈正相关。此外，TAM与术前血清VEGF和VEGF-C水平相关，在共培养系统中，巨噬细胞中VEGF和VEGF-C蛋白表达上调，巨噬细胞中NF-κ B通路的抑制诱导巨噬细胞和GC细胞中VEGF和VEGF-C表达显著降低（均P <0.05）。
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-kappa B pathway in macrophages induced a significant reduction in the expression of VEGF and VEGF-C in both macrophages and GC cells (all P?