HGF antagonist (HGF/NK4) gene therapy for pancreatobiliary cancer.

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Injured peritoneum is susceptible for cancer implantation and metastasis. One reason of the susceptibility is HGF production in the wounded tissue. The wounding causes inflammation, angiogenesis and granulation tissue. 1. We established a model of the metastasis in the wounded site, and examined the protection of implantation and metastasis of the biliary cancer cells by HGF antagonist and the biogel film. 2. HGF mRNA was stimulated in the tissue for 5 days after wounding, but the nature of cells producing HGF could not be determined. 3. A gallbladder cancer cell line, GB-d 1, expressed HGF receptor and responded to extrinsic HGF, but other cancer cells derived from malignant ascites did not show the wound-site specificity. 4. Biogel membranes (hyaluronic acid, oxidated cellulose) covering the wound protected metastasis of the cancer cells. The hyaluronate membrane disappeared within almost 7 days after the wounding and did not disturb wound healing processes. 5. Adenovirus carrying HGF antagonist (HGF/NK4) gene suppressed metastasis in the wounded site of the peritoneum. Substantial amount of antagonist was detected both in cancer cells and peritoneal mesothelial cells in vitro. 6. Angiogenesis in the wounded sites was examined by immunohistochemical methods, but the apparent suppression of tumor angiogenesis was not detected.