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 coagulationfactor-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)-b high , tumor necrosis factor (TNF)-a 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. (Cancer Sci 2011; 102: 336-342) D espite its decreasing incidence, gastric cancer (GC) is still the second leading cause of cancer-related death worldwide, particularly in Asian countries.(1) Peritoneal metastasis is the most frequent event in recurrent GC and occurs in 34% of patients with recurrence, even after curative resection of the primary tumor.(2) Therefore, new approaches to the treatment of metastatic GC have become a hot topic. In addition to clonal selection and the predetermined metastatic potential of cancer cells, there is increasing evidence that the microenvironment modifies cancer cell metastasis.(3-6) Thus, one approach to the treatment of metastatic GC is to identify novel targets based on cancer cell-tumor microenvironment interactions. (7)(8)(9)(10)(11) Tumor stroma consists of activated fibroblasts (myofibroblasts) and smooth muscle, endothelial and inflammatory cells, including macrophages. Macrophages that migrate to tumor stroma are called tumor-associated macrophages (TAM). The role of TAM in tumor progression is complicated. Although activated macrophages might have antitumor activity, tumor cells are reported to escape the antitumor activity of TAM.(...