Neuropilin-1 is an important therapeutic target in pancreatic cancer
| Project/Area Number |
21791310
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Nippon Medical School |
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Principal Investigator |
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | neuropilin-1 / 膵癌 |
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| Research Abstract |
Neuropilin-1(Np-1) is a co-receptor for VEGF-A that is overexpressed in PDAC, but its role in PDAC is not clearly defined. PANC-1 pancreatic cancer cells, which express high levels of Np-1, were transfected with the Np-1 antisense cDNA. By comparison with sham transfected cells, Np-1 antisense expressing clones(Np-1AS) exhibited decreased adhesion and invasiveness. Np-1 associated with integrin β1, and integrin β1 blockade attenuated adhesion, mimicking the effects observed in Np-1AS clones. Furthermore, HGF promoted cell invasion in PANC-1 cells, and this effect was dependent on Np-1.Conversely, COLO-357 pancreatic cancer cells, which express low levels of Np-1, were stably transfected with the Np-1 cDNA. Overexpression of Np-1 was associated with enhanced invasiveness in response to HGF, and these effects could be abolished either by siRNA-mediated down-regulation of c-Met, or by an anti-Np-1 antibody. Np-1 associated with c-Met, and this association occurred on the plasma membrane. Moreover, HGF promoted the internalization of Np-1-c-Met complex. Np-1 is a co-receptor of integrin β1 and c-Met that promotes pancreatic cancer cell adhesion and invasion. Targeting Np-1 may lead to novel therapeutic strategies in PDAC.
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Report
(4 results)
Research Products
(8 results)
