| Project/Area Number |
18K16764
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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 56040:Obstetrics and gynecology-related
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 絨毛癌 / 化学療法抵抗性 / 遠隔転移 / 細胞接着 / LAMP-2 / 転移 |
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| Outline of Final Research Achievements |
This study was performed to investigate the function of LAMP-2 in choriocarcinoma adhesion, invasion and metastasis in order to establish the basis of new therapeutic methods targeting LAMP-2 and improve the prognosis of choriocarcinoma. LAMP-2 was observed in the cell surface membrane of some choriocarcinoma cell lines and tumor cells of choriocarcinoma tissue. Cell surface membrane LAMP-2 knockout decreased cell adhesion and invasion in choriocarcinoma cells. Conversely, cell surface membrane LAMP-2A overexpression increased cell adhesion and invasion. Experiments in the presence of galectins revealed that abundant N-glycans bound to the peptide core of the luminal side of the cell surface membrane LAMP-2 mediated cell adhesion of choriocarcinoma cells by interacting with galectins in the extracellular matrix (ECM). Cell surface membrane LAMP-2 contributes to the malignancy of choriocarcinoma by promoting cell adhesion with the ECM via abundant N-glycans.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、絨毛癌細胞株、及び、実際の絨毛癌組織の細胞膜におけるLAMP-2の発現プロファイルが明らかとなった。また、絨毛癌の細胞膜に発現しているLAMP-2が、その豊富な糖鎖を介して、コラーゲン、フィブロネクチンといた細胞外マトリックスへの接着を促進し、絨毛癌の接着、浸潤、転移に促進的に作用しているのが明らかとなり、LAMP-2が新規の絨毛癌遠隔転移抑制治療の標的となることが示され、LAMP-2を標的とした創薬基盤の基礎を確立することできた。以上の研究成果は、国際学術誌に掲載され、学術的、社会的意義は大きく、難治性絨毛癌の治療成績向上に貢献しうると考えられる。
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