| Project/Area Number |
18K15064
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49010:Pathological biochemistry-related
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| Research Institution | Osaka University |
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Principal Investigator |
KIMURA HIROKAZU 大阪大学, 医学系研究科, 特任助教(常勤) (60595370)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | CKAP4 / DKK1 / エクソソーム / コンパニオン診断 / 腫瘍マーカー |
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| Outline of Final Research Achievements |
In this study, the translocation mechanism of CKAP4, a novel receptor of secreted protein DKK1, to exosome was analyzed. Among many genes associated with exosome biosynthesis, it was revealed that ALIX, Rab27a, Rab27b, VPS26a, and VPS35 are involved in translocation of CKAP4 to exosome. Furthermore, CKAP4 in exosome from serum of patients with pancreatic cancer was measured. Serum CKAP4 levels of immunohistochemically CKAP4-positive cases were significantly higher than those of CKAP4-negative cases and healthy control individuals. Expression levels of CKAP4 in exosome were high in preoperative sera, whereas it was greatly reduced in postoperative sera. These results suggest that CKAP4 secreted with exosomes in serum may represent a biomarker for pancreatic cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
難治性がんである膵がんにおいて新規治療法が求められており、これまでにDKK1-CKAP4シグナルが膵がんの新規治療標的になりうることを明らかにしている。本研究では、CKAP4のエクソソームへの移行メカニズムを明らかにし、血清エクソソーム中CKAP4の測定法を開発した。さらに、血清CKAP4が膵がん症例でCKAP4が発現する症例（DKK1-CKAP4シグナルが活性化する可能性がある症例）を同定するためのコンパニオン診断薬となりうることを明らかした。
本研究成果は、DKK1-CKAP4シグナルを標的としたがんの新規診断法および治療法の開発につながる可能性があり、その社会的意義は大きい。
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