2004 Fiscal Year Final Research Report Summary
Analyses for new genes related to invasion and metastases of human pancreatic cancer cell
| Project/Area Number |
15591415
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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 (2004)
宮崎医科大学 (2003) |
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Principal Investigator |
JIMI Sei-ichiro University of Miyazaki, Dept.Surgery 1, Assistant Professor, 医学部, 助手 (90363598)
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| Co-Investigator(Kenkyū-buntansha) |
ETO Tadaaki University of Miyazaki, Dept.Surgery 1, Assistant Professor, 医学部, 助手 (30322316)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Pancreatic cancer cell / metastasis invasion / Thrombin / PAR-1 / Vitronectin |
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| Research Abstract |
1)Proteinase-activated receptor-1(PAR-1) has been reported to be related to the invasion and metastasis. PAR-1 is a G-protein coupled, which couples 7 times to a trans-membrane type receptor. The N-terminal extracellular component of PAR-1 was cleaved by thrombin and PAR-1 was activated by the self-binding of the N-terminal component. The mRNA expression of PAR-1 on cancer cells and its biological significance is still not clear. We examined the mRNA expression of PAR-1 by real time-PCR in SUIT-2 human pancreatic cancer cell line and its sublines, which were established in our laboratory. We examined both cell growth and cell adhesion to the extracellular matrix of these cell lines by an MTT assay. We studied the effect of a PAR-1 agonist, TRAP-6, and a PAR-1 antagonist, SCH79797, on the cell adhesion to vitronectin. The mRNA expression of PAR-1 was confirmed in all our cell lines. The cell growth and cell adhesion were enhanced by thrombin in almost all cell lines, while they were activated by TRAP-6 and inhibited by SCH79797. The effect of thrombin activation on PAR-1 was found to be related to both pancreatic cancer cell growth and cell adhesion. We have a plan to perform further analyses to the mechanisms of invasion and metastases of these cell lines.
2)We established a new human pancreatic cancer cell line, named SUIT-4. This cell line formed a subcutaneous tumor in the nude mouse, which was histologically moderately differentiated adenocarcinoma. Six of 21 mice demonstrated lymph node metastasis and 4 showed lung metastases. This cell line also had a high metastatic potential (Ref.1). We intend to analyze the molecular mechanisms of invasion and metastases in these cell lines.
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