The clarification of tumor microenvironment in neuroblastoma focused on aldehyde dehydrogenase 1A2

• Project/Area Number: 19K17331
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Kobe University
• Principal Investigator: Uemura Suguru 神戸大学, 医学部附属病院, 助教 (40814348)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 神経芽腫 / ALDH / がん幹細胞 / ALDH1A2 / がん微小環境

Outline of Research at the Start

ALDH1A2をノックダウンした細胞と過剰発現した細胞間で分泌量の異なる分子を質量解析を用いて同定する。また同定した分子の神経芽腫細胞における発現および機能解析を培養した神経芽腫細胞からRNAを抽出して、リアルタイムPCRによって同定した分子の発現を解析していく。

Outline of Final Research Achievements

Previously, we reported that an isoform of aldehyde dehydrogenase (ALDH), ALDH1A2, was highly expressed in cancer stem cells (CSC) of neuroblastoma (NB), regulated their proliferation and differentiation, and its high expression was associated with the poor prognosis of NB patients. In the present study, we tried to identify the secreted molecules from ALDH1A2 overexpressed NB cells. Accordingly, the secretion of nucleoside diphosphate kinase 1 (NME1) was highly elevated in ALDH1A2 overexpressed NB cells.

Academic Significance and Societal Importance of the Research Achievements

神経芽腫の再発はがん幹細胞(CSC)に由来すると考えられている。CSCマーカーであるアルデヒド脱水素酵素(ALDH)は、ヒトでは19のアイソフォームを有するが、その中でもALDH1A2は神経芽腫CSCにおいて発現が亢進し、その予後と関連する。本研究では、ALDH1A2を高発現した神経芽腫細胞からNME1という核酸代謝に関わる蛋白の分泌が亢進していることを明らかにした。血清NME1濃度は、MYC-N増幅神経芽腫患者で高く、患者予後と相関することが報告されており、神経芽腫再発のメカニズムに関わっていると考えられる。

Research Products

• [Journal Article] Limited correlation between tumor markers and minimal residual disease detected by seven neuroblastoma-associated mRNAs in high-risk neuroblastoma patients (2021)
  • Author(s): Suguru Uemura, Kyaw San Lin, Khin Kyae Mon Thwin, Naoko Nakatani, Toshiaki Ishida, Nobuyuki Yamamoto, Akihiro Tamura, Atsuro Saito, Takeshi Mori, Daiichiro Hasegawa, Yoshiyuki Kosaka, Nanako Nino, China Nagano, Satoru Takafuji, Kazumoto Iijima, Noriyuki Nishimura
  • Journal Title: Mol Clin Oncol Volume: 15 Issue: 1 Pages: 137-137
  • DOI: 10.3892/mco.2021.2299
  • NAID: 120007098982
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Minimal residual disease in high-risk neuroblastoma shows a dynamic and disease burden-dependent correlation between bone marrow and peripheral blood (2021)
  • Author(s): Kyaw San Lin
  • Journal Title: Transl Oncol Volume: 14 Issue: 8 Pages: 101019-101019
  • DOI: 10.1016/j.tranon.2021.101019
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Level of Seven Neuroblastoma-Associated mRNAs Detected by Droplet Digital PCR Is Associated With Tumor Relapse/Regrowth of High-Risk Neuroblastoma Patients (2020)
  • Author(s): Khin K M Thwin
  • Journal Title: J Mol Diagn . Volume: 22 Issue: 2 Pages: 236-246
  • DOI: 10.1016/j.jmoldx.2019.10.012
  • Peer Reviewed / Open Access
• [Journal Article] Dynamics of Minimal Residual Disease in Neuroblastoma Patients (2019)
  • Author(s): Suguru Uemura
  • Journal Title: Front Oncol Volume: 9 Pages: 455-455
  • DOI: 10.3389/fonc.2019.00455
  • NAID: 120006645720
  • Peer Reviewed / Open Access
• [Presentation] Prognostic values of tumor markers and minimal residual disease detected by 7NB-mRNAs ddPCR assay for high-risk neuroblastoma patients (2020)
  • Author(s): 植村優
  • Organizer: 日本小児血液がん学会