| Project/Area Number |
16K10561
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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 | Hokkaido University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
西村 紳一郎 北海道大学, 先端生命科学研究院, 教授 (00183898)
島田 慎吾 北海道大学, 医学研究院, 特任助教 (40755576)
若山 顕治 北海道大学, 医学研究院, 客員研究員 (50646544)
武冨 紹信 北海道大学, 医学研究院, 教授 (70363364)
横尾 英樹 旭川医科大学, 医学部, 准教授 (70399947)
折茂 達也 北海道大学, 医学研究院, 特任助教 (80711861)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 糖鎖 / 浸潤 / 転移 / 肝細胞癌 / 外科 |
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| Outline of Final Research Achievements |
We investigated the correlation between alterations in N-glycans and invasiveness by u-PA and EMT. Expression of u-PA and E-glycans/N-cadherin were analyzed by Western blotting in hepatocellular carcinoma (HCC) cell lines. u-PA were knocked down by RNA interference and u-PA was overexpressed in HCC cells using lentiviral vectors. We performed a glycoblotting-assisted MALDI-TOF/MS-based quantitative analysis of HCC cell lines in which invasiveness was altered. The expression of N-glycans, including a form with m/z=1851 and 2521, was changed according to invasiveness controlled by knockdown and overexpression of u-PA expression. These two N-glycans were common in the comparative analysis between HLE with low E-Cadherin expression and HepG2 with high expression. Conclusion: In HCC cells, N-glycosylation is an important factor controlling invasiveness by u-PA and EMT related with E-Cadherin and N-Cadherin. These glycomic alteration may be useful for evaluation of tumor malignancy.
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| Academic Significance and Societal Importance of the Research Achievements |
肝癌培養細胞を用い、網羅的糖鎖解析を行い、u-PAと上皮間葉転換EMTに関連する浸潤能に関与する特異的糖鎖1851m/z、2521m/zが浸潤能変化に検出できた。これらの糖鎖はu-PA、E-Cadherin、N-Cadherinの発現の変化に伴い変化した。これらから癌悪性度変化に関連する糖鎖が検出され、既存のAFP 、AFP-L3、PIVKA-IIと違った糖鎖という視点から肝細胞癌悪性度を評価できる新規バイオマーカーとなり得、これらの糖鎖に関与する糖転移酵素阻害剤を合成できれば、浸潤制御、上皮間葉転換EMT制御ができ、予後延長の可能性があり、創薬の点からも癌治療に大きく貢献できると確信する。
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