Peritoneal dissemination is a common cause of the recurrence of gastric or pancreatic cancer after patients have undergone surgery. The presence of peritoneal metastasis after surgery affects the prognosis of patients with gastric or pancreatic cancer. Very little is known about the biochemical processes involved in the initial attachment of cancer cells to peritoneal mesothelial cells. We conducted in vitro and in vivo studies to assess the role of adhesion molecules in this process, using 5 cell lines derived from human gastric and pancreatic cancers. NUGC-4 and SW1990 cells, which disseminate earlier than the other 3 types of cancer cells after inoculation into the abdominal cavity of nude mice, express large amounts of CD44H. We found that NUGC-4 and SW1990 cells adhere to monolayers of mesothelial cells more firmly than the other cell lines, as shown by adhesion assays performed at 4 degrees C. The adhesion of NUGC-4 and SW1990 cells to mesothelial cells was partially inhibited by antibodies against CD44H or the beta(1) subunit of integrin, and they almost completely blocked adhesion when these 2 antibodies were used in combination in vitro. These 2 antibodies also inhibited the peritoneal metastasis of NUGC-4 and SW1990 cells and prolonged their mean survival time in vivo. These findings suggest that CD44H and beta(1) integrin play important roles in the initial attachment of gastric and pancreatic cancer cells to mesothelial cells. Our results suggest that changes in the expression of CD44H and beta(1) integrin in cancer cells is associated with their ability to adhere to peritoneal mesothelial cells, and thus with the peritoneal metastatic ability of gastric and pancreatic cancer cells. Therefore, the expression of CD44H and beta(1) integrin in gastric and pancreatic cancers could be used as prognostic indicators of peritoneal metastasis. It is possible that a treatment strategy that interferes with the functions of CD44H or beta(1) integrin may result in decreased intra-abdominal spread of cancer.

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