Investigation about LAMP-2 which could be a noble therapeutic target against choriocarcinoma

Research Project

Project/Area Number	18K16764
Research Category	Grant-in-Aid for Early-Career Scientists
Allocation Type	Multi-year Fund
Review Section	Basic Section 56040:Obstetrics and gynecology-related
Research Institution	Nagoya University
Principal Investigator	Nishino Kimiiro 名古屋大学, 医学部附属病院, 助教 (80801448)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
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)
Keywords	絨毛癌 / 化学療法抵抗性 / 遠隔転移 / 細胞接着 / LAMP-2 / 転移
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.
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。