Analysis of cleavage fragments produced by proteolysis on cancer cell membrane
| Project/Area Number |
17K09027
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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 |
Laboratory medicine
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| Research Institution | Kanagawa Cancer Center Research Institute |
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Principal Investigator |
KOSHIKAWA NAOHIKO 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), 臨床研究所, 部長 (70334282)
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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: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 膵癌 / プロセシング / MT1-MMP / HB-EGF / EphA2 / 膜蛋白質 / 膜型メタロプロテアーゼ / 基質 / 限定分解（プロセシング） / プロセシング断片 / ErbB受容体リガンド / がん化促進因子 / バイオマーカー / 癌 / 診断 / 膵臓癌 |
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| Outline of Final Research Achievements |
An early detection method for pancreatic cancer has not been established so far. In this study, we focused on the proteolytic fragment of substrates of membrane-type-1 matrix metalloprotease (MT1-MMP), which is important for the malignant progression of pancreatic. In this study, we made monoclonal antibodies to the proteolytic fragments of MT1-MMP substrates, heparin-binding EGF-like growth factor, HB-EGF and EphA2, and established quantitative ELISA assays for the fragments. As the results, the detection sensitivity of the HB-EGF fragment was not sufficient and required further improvement. In contrast, the serum levels of EphA2 fragment in the patient with pancreatic cancer including an early stage was a significantly higher than that of healthy donors. These results suggest that the EphA2 fragment could be a new biomarker for early pancreatic cancer diagnosis.
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| Academic Significance and Societal Importance of the Research Achievements |
膵癌は早期診断、早期治療以外に完治を見込めない難治癌である。しかし、現状では早期膵癌を見出すバイオマーカーはない。今回着目したMT1-MMP、EphA2は共に早期の膵癌で高発現していることが報告されていることから、それら相互作用としての蛋白分解で生じる基質断片は早期の膵癌の存在を示す重要なバイオマーカーになる可能性をもつ。今後、多検体血清を用いた臨床研究により、これら分解断片の早期膵癌のバオマーカーとしての有用性を明らかとすることが必要となる。
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Report
(4 results)
Research Products
(26 results)
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[Journal Article] Vasoactive Intestinal Peptide Derived From Liver Mesenchymal Cells Mediates Tight Junction Assembly in Mouse Intrahepatic Bile Ducts2020
Author(s)
Sato A, Kakinuma S, Miyoshi M, Kamiya A, Tsunoda T, Kaneko S, Tsuchiya J, Shimizu T, Takeichi E, Nitta S, Kawai-Kitahata F, Murakawa M, Itsui Y, Nakagawa M, Azuma S, Koshikawa N, Seiki S, Nakauchi H, Asahina Y, Watanabe M.
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Journal Title
Hepatology Communications
Volume: 4
Issue: 2
Pages: 235-254
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Serum monomeric laminin-γ2 as a novel biomarker for hepatocellular carcinoma.2017
Author(s)
Kiyokawa H, Yasuda H, Oikawa R, Okuse C, Matsumoto N, Ikeda H, Watanabe T, Yamamoto H, Itoh F, Otsubo T, Yoshimura T, Yoshida E, Nakagawa M, Koshikawa N, Seiki M.
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Journal Title
Cancer Science
Volume: 108
Issue: 7
Pages: 1432-1439
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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