Basic research for the development of personalized therapeutic strategies against a rare renal cell carcinoma

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07236
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kumamoto University
• Principal Investigator: KADOMATSU Tsuyoshi 熊本大学, 大学院生命科学研究部(医), 講師 (90555757)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 腎細胞がん / ANGPTL2 / 尿中バイオマーカー / miRNA / がん免疫

Outline of Final Research Achievements

In this study, we challenged to identify urinary biomarkers for early diagnosis of Xp11.2 translocation renal cell carcinoma (tRCC) and examined molecular mechanisms underlying the development and progression of Xp11.2 translocation renal cell carcinoma. Our results showed that miR-204-5p in urinary exosomes could be a useful biomarker for early diagnosis of patients with Xp11.2 tRCC. We also demonstrated that tumor cell-derived ANGPTL2 accelerates the progression of Xp11.2 tRCC, suggesting that ANGPTL2 signaling could be a novel therapeutic target. Moreover, we showed that tumor stroma-derived ANGPTL2 suppresses tumor progression by facilitating the activation of anti-tumor immune responses.

Free Research Field

分子遺伝学

Academic Significance and Societal Importance of the Research Achievements

本研究では、稀少がんであるが故に治療法や診断マーカーの研究開発が困難なXp11.2転座型腎細胞がんについて、そのモデルマウスを独自に開発し、早期診断に利用可能な新規バイオマーカーや新規治療標的分子を解明するなど、その成果はXp11.2転座型腎細胞がんの個別化治療戦略の確立に寄与するものである。さらに、本研究の成果は、ANGPTL2シグナルを介した抗腫瘍免疫応答制御の解明といった学術的意義も有する。