Elucidation of leading PSC induced basement membrane destruction mechanism and development of the regulating method by using pancreatic organoids
Project/Area Number |
17H04284
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Digestive surgery
|
Research Institution | Kyushu University |
Principal Investigator |
|
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)
|
Project Period (FY) |
2017-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
|
Keywords | 膵癌 / 膵星細胞 / リーディングセル / 基底膜破壊 / MMP2 / MT1-MMP / 膵臓癌 / 基底膜 / 癌関連マクロファージ / オルガノイド / PSC / 膵オルガノイド |
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.
|
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。
|
Report
(4 results)
Research Products
(10 results)
-
-
-
[Presentation] BM-Derived Cells Destruct Basement Membrane and Induce Local Invasion of Pancreatic Cancer2019
Author(s)
Iwamoto C, Ohuchida K, Ando Y, Shinkawa T, Ohtsubo Y, Shindo K, Moriyama T, Nakata K, Miyawaki K, Ohtsuka T, Akashi K, Eto M, Nakamura M
Organizer
The 50th Annual Meeting of the American Pancreatic Association(APA)
Related Report
Int'l Joint Research
-
-
-
-
[Presentation] Endo180 Expression and Histologic Categorization in Cancer Stroma is an Independent Prognostic Index in Pancreatic Cancer.2018
Author(s)
Koikawa K, Ohuchida K, Yonenaga A, Sagara A, Ando Y, Kibe S, Takesue S,Nakayama H, Iwamoto C, Shindo K, Moriyama T, Nakata K, Miyasaka Y, Ohtsuka T, Mizumoto K, Nakamura M
Organizer
49th Annual Meeting of the APA
Related Report
Int'l Joint Research
-
[Presentation] Basement membrane destruction by pancreatic stellate cells leads to local invasion in pancreatic ductal adenocarcinoma2018
Author(s)
Koikawa K, Ohuchida K, Ando Y, Kibe S, Nakayama H, Takesue S, Endo S, Abe T, Okumura T, Iwamoto C, Shindo K, Moriyama T, Nakata K, Miyasaka Y, Ohtsuka T, Nagai E, Mizumoto K, Hashizume M, Nakamura M
Organizer
Pancreas 2018
Related Report
Int'l Joint Research
-
-
[Presentation] Pancreatic organoids elucidate the new mechanisms of pancreatic cancer local invasion2017
Author(s)
Koikawa K, Ohuchida K, Ando Y, Kibe S, Nakayama H, Takesue S, Yan Z, Abe T, Okumura T, Iwamoto C, Moriyama T, Nakata K, Miyasaka Y, Okabe Y, Ohtsuka T, Mizumoto K, Nakamura M
Organizer
The 48th Annual Meeting of The American Pancreatic Association
Related Report
Int'l Joint Research