2004 Fiscal Year Final Research Report Summary
Mechanisms responsible for peritoneal metastasis and lymph node metastasis in scirrhous gastric carcinoma
| Project/Area Number |
13470260
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Osaka City University |
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Principal Investigator |
HIRAKAWA Kosei Osaka City University, Graduate School of Medicine Department :Surgical Oncology, Professor, 大学院・医学研究科, 教授 (40188652)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIRO Masakazu Osaka City University, Graduate School of Medicine Department : Surgical Oncology, Lecturer, 大学院・医学研究科, 講師 (60305638)
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| Project Period (FY) |
2001 – 2004
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| Keywords | growth activity / fibroblasts / ICAM1 / Peritoneal metastasis / scirrhous gastric carcinoma / lymph node metastasis |
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| Research Abstract |
Prognosis of advanced stage gastric carcinoma remains poor because of the frequent incidence of metastasis. We examined the effect of adhesion polypeptides on the adhesion and invasiveness of gastric cancer cell lines. Peritoneal-seeding cell line, OCUM-2MD3, was established from a poorly seeding human scirrhous gastric carcinoma cell line, OCUM-2M. Both α2β1 and α3β1 integrin expression was markedly increased on OCUM-2MD3 cells compared with OCUM-2M cells, and the adhesion ability of OCUM-2MD3 cells to the extracellular matrix (ECM) was also significantly higher than that of OCUM-2M cells. The adhesion polypeptides, YIGSR and RGD significantly inhibited the adhesion of OCUM-2MD3 cells to the submesothelial ECM, while not inhibiting the adhesiveness of OCUM-2M cells and two well differentiated human gastric cell lines, MKN-28 and MKN-74. The YIGSR and RGD peptides also significantly inhibited the invasiveness of OCUM-2MD3 cells. The survival of nude mice with peritoneal dissemination g
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iven YIGSR sequence intraperitoneally was obviously longer than that of untreated mice. These polypeptides appear to block the binding of integrins, which are expressed on OCUM-2MD3 cells, to the submesothelial ECM. The peritoneal injection of adhesion polypeptides may be a new therapy against the dissemination of scirrhous gastric cancer, and may be useful for the prevention of dissemination in high-risk patients.
We transfected ICAM-1 genes into gastric cancer cell line, 2MLN, and analyzed the effect on the lymph node metastasis of the transduction of ICAM-1 in vitro and in vivo. Lymph node metastases caused by 2MLN/ICAM cells were recognized as being fewer in number and smaller, while many lymph node metastases caused by 2MLN cells were recognized. These findings indicate that ICAM-1 gene might be a tumor suppressor gene that is important for lymph node metastasis, and that ICAM-1 gene transduction could prove to be an effective gene therapy for lymph node metastasis of gastric cancer. Less
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Research Products
(12 results)
