Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, China.
Cancer Sci. 2011 Feb;102(2):336-42. doi: 10.1111/j.1349-7006.2010.01795.x. Epub 2010 Dec 7.
Abundant macrophage infiltration and increased expression of coagulation factors have been observed in cancer patients. The aim of the present study was to determine how the interaction between activated coagulation factors and monocytes/macrophages contributes to gastric cancer (GC) cell migration and invasion. We assessed cytokine/chemokine production of coagulation-factor-treated macrophages by ELISA. The effects of the interaction between coagulation factors and tumor-associated macrophages (TAM) on GC cell migration and invasion were determined by in vitro migration and invasion assay. In addition, we used an in vitro co-culture system of GC cells/TAM treated by coagulation factors to evaluate the effect of coagulation factor/TAM interaction on the human umbilical vein endothelial cell line (HUVEC). We found that the M2-like phenotype of interleukin (IL)-4(high), IL-10(high), transforming growth factor (TGF)-β(high), tumor necrosis factor (TNF)-α(high) was exhibited when the human monocytic cell line THP-1 was stimulated by coagulation factors III (TF), VIIa (FVIIa) and XIIa (FXIIa). For the migration assay, the GC cells (BGC-823 or SGC-7901) that were co-cultured with activated coagulation factor/TAM both showed increased migration. For the invasion assay, both BGC-823 and SGC-7901 cells co-cultured with TF/TAM showed increased invasion. We also found that TAM activated by coagulation factors could induce vascular endothelial growth factor/MMP-9 expression, which could promote invasion of GC cells. The HUVEC co-cultured with TAM (PMA-treated THP-1 macrophages co-cultured with GC cells) expressed high levels of FXIIa. In conclusion, coagulation factors might facilitate GC cell migration and invasion by transforming macrophages toward TAM-like cells. Interaction of coagulation factors and TAM mediates migration and invasion of GC.
大量的巨噬细胞浸润和凝血因子表达增加在癌症患者中被观察到。本研究旨在确定激活的凝血因子与单核细胞/巨噬细胞的相互作用如何促进胃癌（GC）细胞的迁移和侵袭。我们通过 ELISA 评估了凝血因子处理的巨噬细胞细胞因子/趋化因子的产生。通过体外迁移和侵袭实验，确定了凝血因子与肿瘤相关巨噬细胞（TAM）之间的相互作用对 GC 细胞迁移和侵袭的影响。此外，我们使用了凝血因子处理的 GC 细胞/TAM 的体外共培养系统来评估凝血因子/TAM 相互作用对人脐静脉内皮细胞系（HUVEC）的影响。我们发现，当人单核细胞系 THP-1 被凝血因子 III（TF）、VIIa（FVIIa）和 XIIa（FXIIa）刺激时，表现出白细胞介素（IL）-4（高）、IL-10（高）、转化生长因子（TGF）-β（高）、肿瘤坏死因子（TNF）-α（高）的 M2 样表型。对于迁移实验，与活化凝血因子共培养的 GC 细胞（BGC-823 或 SGC-7901）均表现出迁移增加。对于侵袭实验，与 TF/TAM 共培养的 BGC-823 和 SGC-7901 细胞均表现出侵袭增加。我们还发现，凝血因子激活的 TAM 可以诱导血管内皮生长因子/MMP-9 的表达，从而促进 GC 细胞的侵袭。与 TAM（用佛波醇酯处理的 THP-1 巨噬细胞与 GC 细胞共培养）共培养的 HUVEC 表达高水平的 FXIIa。总之，凝血因子可能通过将巨噬细胞转化为 TAM 样细胞来促进 GC 细胞的迁移和侵袭。凝血因子与 TAM 的相互作用介导了 GC 的迁移和侵袭。
