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.


CONCLUSIONS
TIMP-1 demonstrated an inhibitory effect on angiogenesis, and may be worthwhile investigating for use as a future therapy for peritoneal dissemination.
Miyagi
Motoshi
M
Department of Surgery, Kurume University, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.
Aoyagi
Keishiro
K
Kato
Seiya
S
Shirouzu
Kazuo
K
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics / Q000556:secondary*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010534:Peritoneal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000556:secondary*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D019715:Tissue Inhibitor of Metalloproteinase-1