Cancer‐associated orthotopic myofibroblasts stimulates the motility of gastric carcinoma cells

摘要

Tumor progression has been recognized as the product of evolving crosstalk between cancer cells and the surrounding stromal cells. Cancer‐associated orthotopic myofibroblasts may be linked to the progression of gastric carcinomas. To understand the significance of orthotopic myofibroblasts, we examined the effects of cancer‐associated orthotopic myofibroblasts on the malignant phenotype of gastric cancer cells. Three human gastric cancer cell lines (OCUM‐2MD3, OCUM‐12, MKN‐45) and four human gastric fibroblast cell lines (cancer‐associated orthotopic fibroblast [CaF]‐29, CaF‐33, normal orthotopic fibroblast [NF]‐29, NF‐33) were used. The cancer‐associated orthotopic fibroblast cell lines CaF‐29 and CaF‐33 were established from a tumoral gastric wall, and normal orthotopic fibroblast NF‐29 and NF‐33 were established from a non‐tumoral gastric wall. Fibroblasts that were α‐smooth muscle actin‐positive were defined as myofibroblasts. We examined the effects of cancer‐associated orthotopic myofibroblasts on the aggressiveness of gastric cancer cells by wound‐healing assay, invasion assay, and RT‐PCR. The ratios of myofibroblasts in CaF‐29 (33%) and CaF‐33 (46%) were significantly (P < 0.001) greater than those in NF‐29 (11%) or NF‐33 (13%). Although all four orthotopic fibroblast lines increased the motility of gastric cancer cells, including migration and invasion ability, the motility‐stimulating activity of cancer‐associated fibroblasts (CaF‐29 and CaF‐33) was significantly higher than that of normal fibroblasts (NF‐29 and NF‐33). These motility‐stimulating activities of cancer‐associated orthotopic fibroblasts were downregulated by Smad2 siRNA treatment and anti‐transforming growth factor‐β neutralizing antibody. These findings suggest that cancer‐associated orthotopic myofibroblasts may play an important role in the progression of gastric cancers and that transforming growth factor‐β produced by myofibroblasts may be one of the factors associated with the aggressiveness of gastric carcinoma cells. (Cancer Sci 2012; 103: 797–805)