The TIMP-1 gene transferred through adenovirus mediation shows a suppressive effect on peritoneal metastases from gastric cancer

Background. It has become clear in recent years that peritoneal metastasis takes place as the result of a multistep process involving attachment, invasion, proliferation, and angiogenesis. The aim of the present study was to evaluate the suppressive effect of tissue inhibitor of metalloproteinase-1 (TIMP-1) gene transfer on peritoneal dissemination. Methods. We established a high-potential peritoneal metastasis cell line (MKN-45P), using the gastric cancer cell line MKN-45, and developed a peritoneal metastasis model in nude mice. The TIMP-1 gene was transferred to MKN-45 or MKN-45P by adenoviral transfection, and we performed an in vitro invasion assay and an in vivo study, using the peritoneal metastasis model. The TIMP-1 transfected group was compared with a non-virus group and a Lac-Z transfected group. Results. The in vitro invasion assay showed that the number of invasive cells was significantly reduced in the TIMP-1 transfected group compared with that in the non-virus group and the Lac-Z transfected group, Moreover, the in vivo studies showed that the number and the weight of the peritoneal nodes in the TIMP-1 transfected group were significantly less than those in the Lac-Z transfected group, and less than those in the non-viral group. No bloody ascites was recognized in the TIMP-1 transfected group. The mean number of tumor vessels in the non-virus group and the Lac-Z group was significantly higher than that in the TIMP-1 group. Conclusion. TIMP-1 demonstrated an inhibitory effect on angiogenesis, and may be worthwhile investigating for use as a future therapy for peritoneal dissemination.