| Project/Area Number |
17K10692
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Niigata University |
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Principal Investigator |
Nakajima Masato 新潟大学, 医歯学総合研究科, 客員研究員 (60588250)
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| Co-Investigator(Kenkyū-buntansha) |
永橋 昌幸 新潟大学, 医歯学総合病院, 研究准教授 (30743918)
若井 俊文 新潟大学, 医歯学系, 教授 (50372470)
坂田 純 新潟大学, 医歯学系, 講師 (70447605)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | スフィンゴシン-1-リン酸 / 脂質メディエーター / 癌微小環境 / 膵癌 / CRISPR/Cas9 / スフィンゴシン‐１‐リン酸 |
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| Outline of Final Research Achievements |
Sphingosine-1-phosphate (S1P) is a lipid mediator that regulates important functions in cancer progression. The aim of this study was to elucidate roles of S1P signaling in the formation of pancreatic cancer microenvironment. We revealed that the S1P level in surgical specimens of pancreatic cancer tissue was significantly higher than that in noncancerous pancreatic tissue. Furthermore, we produced murine pancreatic cancer cell lines in which gene of S1P producing enzyme (SphK1 or SphK2) was knocked out, and compared them with wild type cells. Our study indicated that SphK1 promotes anticancer drug resistance, and that SphK2 is involved in proliferation and progression of pancreatic cancer cells. This study will bring a new perspective in signal transduction pathways involved in the formation of pancreatic cancer microenvironment.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで癌組織中のS1P濃度を測定する方法がなく、癌の発育進展における脂質メディエーターの役割が注目を集める中、手術検体を用いた研究はなされてこなかった。我々は、膵癌手術検体から組織間液を抽出し、質量分析装置を用いて間質液中のS1P濃度を測定することに成功した。さらに培養細胞におけるS1P産生酵素をノックアウトし、野生型細胞との比較を行うことで、S1Pシグナルが癌の微小環境形成ならびに発育進展に関わる可能性を示唆する結果を得た。本研究はS1Pシグナルの膵癌微小環境における役割を検討する上で新たな視点をもたらしたと言える。
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