| Project/Area Number |
16390383
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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 | Nagoya City University |
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Principal Investigator |
MANABE Tadao Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院医学研究科, 教授 (80127141)
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| Co-Investigator(Kenkyū-buntansha) |
OKADA Yuji Nagoya City University, Graduate School of Medical Sciences, Assistant professor, 大学院医学研究科, 講師 (10305550)
TAKAHASHI Hiroki Nagoya City University, Graduate School of Medical Sciences, Research Associate, 大学院医学研究科, 助手 (30381792)
YAMAMOTO Minoru Nagoya City University, Graduate School of Medical Sciences, Research Associate, 大学院医学研究科, 助手 (70347417)
SAWAI Hirozumi Nagoya City University, Graduate School of Medical Sciences, Assistant professor, 大学院医学研究科, 講師 (40336681)
松尾 洋一 名古屋市立大学, 大学院医学研究科, 助手 (40381800)
舟橋 整 名古屋市立大学, 大学院・医学研究科, 助手 (10347411)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2006: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2005: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2004: ¥5,900,000 (Direct Cost: ¥5,900,000)
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| Keywords | neurotrophic factor / pancreatic cancer / integrin / interleukin-lalpha / NF-kappaB / integtin |
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| Research Abstract |
We previously reported that the neurotrophic factor, GDNF, has an important role in the invasive capability of pancreatic cancer cells. Furthermore, we confirmed that increased IL-lalpha expression is a feature of liver-metastatic pancreatic cancer cell lines and that IL-lalpha enhances adhesion molecule integrins expression and metastatic potential in pancreatic cancer cell lines via IL-1 receptor type I (IL-1RI). The aims of this study were to identify the role of GDNF and inflammatory cytokines for pancreatic cancer cell proliferative, adhesive, and invasive capabilities.
We report the results that we acquired till now as follows.
1. GDNF and IL-lalpha significantly enhanced the expression of a6β1 and a5β1-integrins through the activation of transcription factors such as NF-kB and AP-1.
2. In all intrapancreatic nerves GDNF was expressed strongly. In pancreatic cancer tissues, the expression of RET was stronger than that seen in normal ductal cells and was significantly related to the survival rate after resection and lymphatic invasion.
3. Alteration of ILK kinase activity controlled p38 MAPK phosphorylation with subsequent regulation of pancreatic cancer cell adhesion and invasion. Overexpressed ILK enhances the p38 MAPK phosphorylation strongly through GSK-3 activation which promotes aggressive capabilities of pancreatic cancer cells. In immunohistochemical analysis, statistically significant association between strong expression of ILK and poor prognosis of pancreatic cancer patients were observed.
4. FAK activation correlated with the activation of Ras/ERK signaling pathways in pancreatic cancer cells and activation of these signaling pathways can be inhibited by knockdown of FAK expression with siRNA, consistent with the inhibition of adhesive and invasive capabilities of pancreatic cancer cells.
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