2019 Fiscal Year Final Research Report
Elucidation of leading PSC induced basement membrane destruction mechanism and development of the regulating method by using pancreatic organoids
Project/Area Number |
17H04284
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Digestive surgery
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Research Institution | Kyushu University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
岩本 千佳 九州大学, 大学病院, 特任助教 (10752842)
大塚 隆生 九州大学, 医学研究院, 准教授 (20372766)
村田 正治 九州大学, 先端医療イノベーションセンター, 特任教授 (30304744)
藤田 逸人 九州大学, 医学研究院, 助教 (40611281)
池永 直樹 九州大学, 大学病院, 助教 (90759755)
宮坂 義浩 九州大学, 大学病院, 助教 (40507795)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Keywords | 膵癌 / 膵星細胞 / リーディングセル / 基底膜破壊 / MMP2 / MT1-MMP |
Outline of Final Research Achievements |
In this study, we investigated how pancreatic stellate cells (PSCs) disrupt the basement membrane of pancreatic cancer tissue and support the invasion of pancreatic cancer cells by using pancreatic cancer organoids, and aimed to develop a regulating method therefor. Pancreatic cancer organoids formed a basement membrane similar to the pancreatic cancer tissue, and a three-dimensional co-culture model with PSCs revealed that PSCs promoted pancreatic cancer cell invasion through basement membrane destruction in real time observation. In addition, it was clarified through in vitro / in vivo assays by RNA interference that the basement membrane destruction mediated by MMP2 and MT1-MMP of PSCs supported pancreatic cancer cell invasion. In the future, we will identify specific pancreatic stellate cells that function as leading cells and develop a novel method for regulating pancreatic cancer invasion by controlling them.
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Free Research Field |
医歯薬学
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Academic Significance and Societal Importance of the Research Achievements |
膵癌の予後を規定する癌浸潤メカニズムを解明するために、膵星細胞のleading cellとしての機能に着目して研究を行い、膵星細胞がMMP2およびMT1-MMPによる基底膜破壊を介して膵癌細胞浸潤を支持していることを解明した。膵星細胞のleading cellとしての機能を解明した研究はこれまでになく、これらを制御することで膵癌細胞浸潤を抑制する新規の制御法の開発が可能となった。その制御法を確立し臨床応用することによって今後の膵癌患者の予後改善に寄与し得ると考えられる。
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