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

2020 Fiscal Year Final Research Report

• 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
• Keywords: 絨毛癌 / 化学療法抵抗性 / 遠隔転移 / 細胞接着 / LAMP-2

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.

Free Research Field

産婦人科

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。