Tumor-associated macrophages promote angiogenesis and lymphangiogenesis of gastric cancer.

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.