Project/Area Number |
17K16535
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Digestive surgery
|
Research Institution | Kanazawa University |
Principal Investigator |
|
Project Period (FY) |
2017-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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Keywords | 膵癌 / 血管外血小板凝集 / CD44 / 上皮間葉転換 / MicroRNA21 |
Outline of Final Research Achievements |
Little is known about the molecular cytological events involved in extravasated platelet aggregation (EPA) and tumor progression in cancer microenvironment. In this study, we examined the effect of human platelets on pancreatic cancer cells. Co-culture of platelets obtained from healthy volunteers and pancreatic cancer cell lines showed an increase in invasion ability for pancreatic cancer cells, and also decreased in expression of PTEN, a tumor suppressor gene. Moreover, expression of CD44 standard form concerned to adhesion to pancreatic cancer cells for platelets. In addition, expression of the CD44 standard form increased the adhesion between platelets and pancreatic cancer cells, suggesting that CD44 standard form involved in pancreatic cancer cell and platelet adhesion.
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Academic Significance and Societal Importance of the Research Achievements |
膵癌は難治癌の一つとされ、治療成績向上は急務である。これまでの報告では血管内血小板による癌細胞のcloak形成、免疫寛容の報告は認めているが、癌局所での血管外血小板凝集と腫瘍の増殖進展に関する分子細胞学的な事象に関してはほとんど明らかとなっていなかった。本研究では血小板と膵癌の接着、凝集にはCD44 standard fromが重要であることが示唆された。EMTを起こした膵癌細胞を取り囲むようにして存在する血小板は、癌局所において免疫逃避となり、血管内に侵入しやすい状態を形成する。すなわち、pre-metastatic nicheを形成し、浸潤、転移を促進していると推察される。
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