2006 Fiscal Year Final Research Report Summary
Effect of adhesion molecules on invasion of pancreatic cancer cells, including tumor-stromal interaction.
| Project/Area Number |
17591418
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | University of Miyazaki |
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Principal Investigator |
MAEHARA Naoki University of Miyazaki, Faculty of Medicine, Assistant Professor, 医学部, 助手 (30381065)
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| Co-Investigator(Kenkyū-buntansha) |
HIDAKA Hideki University of Miyazaki, Faculty of Medicine, Assistant Professor, 医学部, 助手 (90398264)
OHUCHIDA Jiro University of Miyazaki, Faculty of Medicine, Assistant Professor, 医学部, 助手 (10363590)
NAGANO Motoaki University of Miyazaki, Faculty of Medicine, Clinical Fellow, 医学部, 医員 (50381116)
CHIJIIWA Kazuo University of Miyazaki, Faculty of Medicine, Assistant Professor, 医学部, 教授 (90179945)
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| Project Period (FY) |
2005 – 2006
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| Keywords | pancreatic cancer / thrombin / PAR-1 / adhesion / Vitronectin / Integrin |
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| Research Abstract |
We first analyzed expression of the PAR-1/thrombin receptor in human pancreatic carcinoma cells by RT-PCR. Six distinct types of human pancreatic cancer cell lines expressed varying levels of PAR-1/thrombin receptor, which means that these cancer cells are potential target cells of thrombin.
We next analyzed effects of thrombin on proliferation of pancreatic cancer cells. With the addition of thrombin, proliferation was stimulated in most pancreatic cancer cells. Regulating cell-cycle progression from G1 to S phase, thrombin promotes cell growth by up-regulation of cyclin D3.
The adhesion of tumor cells to the endothelium or extracellular matrix (ECM) is an essential step in the metastatic cascade. We investigated effects of thrombin on the adhesion activity of pancreatic cancer cells to ECMs. There was a correlation between metastatic potential and adhesional activity to ECMs in pancreatic cancer cells. But there was no correlation between metastatic potential and thrombin-induced adhesion. Thrombin especially stimulated the adhesion of cancer cells to Vitronectin and Fibronectin. Promotion of tumor cell adhesion to Vitronectin was observed upon addition of thrombin receptor agonist peptide (TRAP-6). SCH79797, which is a PAR-1 antagonist, effectively antagonized the thrombin-enhanced cell adhesion activity. Thrombin-PAR-1 cascade might play an important role in the adhesion of pancreatic cancer cells to ECMs.
We examined effects of thrombin activation on cell adhesion through integrins, a group of receptors mediating interaction between tumor cells and ECMs. An antibody against 3 1 integrins inhibited the adhesion of tumor cells to Vitronectin induced by thrombin.
These results show that PAR-1/thrombin regulates cellular adhesion and proliferation, and that the thrombin-induced adhesion of pancreatic cancer cells to Vitronectin is regulated by integrin v 3 1 on the tumor cell.
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[Journal Article] Comparative effect of lymph node metastasis classified by the anatomical site or by the number of nodes involved on prognosis of patients with gastric cancer.
Author(s)
Hidaka, H., Eto, T.-A., Maehara, N., Jimi, S.-I., Hotokezaka, M., Chijiiwa, K.
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Journal Title
Hepato-Gastroenterology (in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Surgical Treatment for Gastric GIST with Special Reference to Liver Metastases.
Author(s)
Maehara, N., Chijiiwa, K., Eto, T., Funagayama, M., Uchiyama, S., Nakashima, S., Hidaka, H., Hotokezaka, M.
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Journal Title
Hepato-Gastroenterology (in press)
Description
「研究成果報告書概要(欧文)」より
