| Project/Area Number |
17K10705
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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 | Oita University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
猪股 雅史 大分大学, 医学部, 教授 (60315330)
太田 正之 大分大学, 国際教育研究推進機構, 教授 (80271104)
岩下 幸雄 大分大学, 医学部, 講師 (60534203)
上田 貴威 大分大学, 医学部, 准教授 (30625257)
多田 和裕 大分大学, 医学部, 医員 (50792503)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 膵癌 / レクチン / フコシル化 / FUT / F U T / 糖鎖 |
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| Outline of Final Research Achievements |
This study aimed to identify glycan alterations and their relationship with the malignant potential of PDAC. Using a lectin microarray, we evaluated glycan expression in PDAC samples. Expression of fucosyltransferase 8 (FUT8) was investigated by immunohistochemistry. The role of FUT8 in PDAC invasion and metastasis was confirmed using an in vitro assay and a xenograft peritoneal metastasis mouse model. The microarray data demonstrated that core fucose-binding lectins were higher in carcinoma than in normal pancreatic duct tissues. Similarly, FUT8 protein expression was higher in carcinoma than in normal pancreatic duct tissues. High FUT8 protein expression was associated with lymph-node metastases and relapse-free survival. FUT8 knockdown reduced the invasion in PDAC cell lines and impaired peritoneal metastasis in the xenograft model. This study provide evidence that FUT8 plays a pivotal role in PDAC invasion and metastasis and might be a therapeutic target for this disease.
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| Academic Significance and Societal Importance of the Research Achievements |
膵癌におけるフコシル化とそれを制御するFUTの発現と癌化の関係を検討し、FUT8の発現はリンパ節転移や無再発生存と関連し、膵癌細胞株で浸潤や転移に関わる因子である可能性が示唆された。膵癌は未だ予後不良の疾患で、早期発見や新規治療薬が必要である。今後のさらなる研究は必要であるが、FUTが膵癌の進展に関わる可能性が示されたため、この因子は早期診断のためのマーカーとしての使用や効果的な治療標的分子となりうると考えられる。
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