| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
The adhesion of gastric cancer cells to peritoneum is a key step in the first process of peritoneal dissemination. It has been shown that various cell adhesion molecules, such as integrins, play critical roles in the adhesion. Immunohistochemical analysis of clinical specimens of gastric cancer revealed that VLA-3 (α3β1 integrin) expression is positively correlated with the peritoneal metastatic potential. This observation suggests that VLA-3 integrin may play an important role in the process of peritoneal metastasis of gastric cancer.
In this study, we conducted in vitro and in vivo experiments to assess the role of VLA-3 in the adhesion of cancer cells to peritoneum. The cDNA to human α3 integrins were introduced into K562 leukemic cells, The α3 integrin-transfected cells (K3-9 cells) were found to have higher capacity in the adhesion to mouse peritoneum than the mock transfected cells (KR cells). Furthermore, the adhesion of four human gastric carcinoma cell lines to the peritoneum was partially inhibited by a monoclonal antibody against VLA-3. The expression of laminin 5 and laminin 10/11, high affinity ligands for VLA-3, was examined by the RT-PCR method. The mRNA for laminin 5 and laminin 10/11 was detected in diaphragm and peritoneum, suggesting that these members of the laminin family are involved in the VLA-3-mediated adhesion of cancer cells. In order to evaluate the contribution of VLA-3 integrin in peritoneal dissemination in vivo, K3-9 and KR cells were inoculated into the abdominal cavity of SCID mice, The formation of tumor associated with the peritoneum and diaphragm was observed three weeks after i. p. inoculation of K3-9 cells.
These results strongly suggest that VLA-3 integrin mediates the initial attachment of cancer cells to peritoneum and that the overexpression of VLA-3 on cancer cells promotes the intraperitoneal tumor growth.
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