Novel anti-tumor angiogenesis therapeutic strategy by targeting VEGF signaling pathway through N-myc downstream regulated gene 1 (NDRG1)

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07169
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Kyushu University
• Principal Investigator: Watari Kosuke 九州大学, 薬学研究院, 准教授 (90596834)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: NDRG1 / VEGF / VEGFR2 / PLCγ / 血管新生 / 血管内皮細胞

Outline of Final Research Achievements

Vascular endothelial growth factor (VEGF) is a key regulator of tumor angiogenesis that is essential for tumor growth and progression. The unraveling of the precise mechanisms behind VEGF-induced tumor angiogenic process will further contribute to development of novel and potent anti-cancer therapeutics. We previously reported that N-myc downstream regulated gene 1 (NDRG1) expression levels in cancer cells are closely correlated with tumor angiogenesis and growth, and also that NDRG1 promotes tumor angiogenesis through enhanced VEGF production by tumor-associated macrophages. However, it remains unclear whether NDRG1 expression in vascular endothelial cells (ECs) plays any crucial role in VEGF-A-induced tumor angiogenesis. In our present study, we further ask whether and how NDRG1 in ECs could specifically regulate tumor angiogenesis. We also present our finding of intrinsic importance that NDRG1 functions as an essential factor for VEGF-induced angiogenesis.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

(1)現在臨床応用されている腫瘍血管新生阻害剤はVEGF及びVEGFR2を標的とした抗体薬やマルチキナーゼ阻害剤である。本研究ではNDRG1に着目することで、有用な治療標的であるVEGF特異的なシグナル制御メカニズムを明らかにできる点に大きな特色がある。
(2)病的な血管新生の誘導は、がんのみならず糖尿病性網膜症や関節リウマチなど他の疾病の悪性化にも深く関連している。そのため、本研究で新規VEGFシグナル制御因子としてNDRG1を提示することは、がんを含む様々な疾病の発症や悪性化を予測するバイオマーカーや治療薬の創出にも大きく貢献できると確信している。