| Project/Area Number |
16K11292
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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 |
Ophthalmology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
阿部 晃 札幌医科大学, 医学部, 講師 (70136927)
平岡 美紀 札幌医科大学, 医学部, 講師 (80246983)
日景 史人 札幌医科大学, 医学部, 助教 (30837547)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | リカバリン / 癌関連網膜症 / カベオリン / 自己免疫 / 網膜変性 / 癌異所性発現 / Ｇ蛋白共役受容体 / 腫瘍随伴症候群 / 視細胞 / GRK |
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| Outline of Final Research Achievements |
Cancer-associated retinopathy (CAR) is an ocular manifestation of a paraneoplastic syndrome whereby immunological reactions toward recoverin and other antigens aberrantly expressed in tumor cells is elicited. To elucidate the pathological role of the aberrantly expressed recoverin, we studied the recoverin expression levels in various malignant tumors and the effects of the expressed recoverin on the sensitivity to anti-cancer drugs. Recoverin expression levels were determined by immunohistochemistry with anti-human recoverin monoclonal antibody on multiple tissue arrays obtained from several cancers. In the presence of several anti-cancer drugs, cytotoxicity assay was performed using recoverin positive or negative A549 cells originated from human lung adenocarcinoma. Recoverin immunoreactivities were detected at approximately 10-40% of malignant tumor tissues. Cytotoxic effects by anti-cancer drugs were higher in recoverin-positive A549 cells as compared to recoverin-negative cells.
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| Academic Significance and Societal Importance of the Research Achievements |
リカバリンは視細胞内ではGRK1と共役し明暗順応の制御に関与するが、癌細胞では他のGRKおよびカベオリンと共役し、細胞増殖を制御する可能性を示唆した。また、カベオリン-１の機能として腫瘍増殖・転移・薬物抵抗性のシグナル伝達制御に関連する重要な因子であることが報告されている。これらの報告を踏まえると、本研究結果はリカバリンが腫瘍細胞中でカベオリンと共役し、薬剤抵抗性を制御することを強く示唆する。ゆえにリカバリンの存在は、原発癌に対する抗がん剤の効き目をあげると考えられる。また、カベオリンのように、将来的には各種腫瘍に対する予後マーカーとなりうる可能性がある。
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