Development of a therapeutic strategy for urologic cancers targeting Protein-Coupled Receptor 87

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18118
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Kagawa University
• Principal Investigator: Yoichiro Tohi 香川大学, 医学部附属病院, 助教 (60867290)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: GPR87

Outline of Final Research Achievements

The GPR87 (G protein-coupled receptor 87) is a receptor located on the cell surface and is involved in cell proliferation. Our study aimed to develop a therapeutic strategy for urothelial cancer targeting the tumor cell surface biomarker GPR87. We focused on adeno-associated virus (AAV) vectors because they can deliver genes to have low immunogenicity, and are suitable for introduction into animal models. We cloned the effective siRNA sequence demonstrated by Ad-sh GPR87 vector in bladder cancer cell lines into shRNApAAV-CMV Vector, and after transfection and culturing, we created an adeno-associated virus vector expressing shRNA (AA-shsiGPR87). However, it was found that the efficiency of introducing this AAV into bladder cancer cell line RT112 in vitro was only around 20%. Therefore, we focused on exosomes to achieve better introduction efficiency. We purified AAV-containing exosomes and demonstrated an increase in introduction efficiency compared to conventional AAV.

Free Research Field

Urologic oncology

Academic Significance and Societal Importance of the Research Achievements

腫瘍細胞表面バイオマーカーであるGPR87を標的とする治療戦略の構築は、泌尿器癌の治療において新たなアプローチとなる可能性がある。GPR87の発現は多くの悪性腫瘍にみられるため、泌尿器科領域以外の癌にも応用可能性があり、より効果的かつ個別化された治療が実現できる可能性がある。ただし、遺伝子導入効率の点ではAAVでは不十分であることが明らかになった。よりよい導入効率を目指しexosomeに着目し、AAV-cotaining exosomeを精製を行い、通常のAAVと比較して導入効率の増加を証明した点は遺伝子導入や薬物デリバリーの分野での新たなアプローチの開発につながる可能性がある。