Role of NDRG1 in tumor angiogenesis through activation of tumor-associated macrophages and vascular endothelial cells.

• Project/Area Number: 25830083
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Kyushu University
• Principal Investigator: WATARI Kosuke 九州大学, 薬学研究科(研究院), 助教 (90596834)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: NDRG1 / 血管新生 / マクロファージ / 血管内皮細胞 / VEGF / がん / M-CSF

Outline of Final Research Achievements

N-myc downstream regulated gene 1 (NDRG1) has been known to play pleiotropic roles in cell growth, development and differentiation. We have previously reported that NDRG1 expression levels in cancer cells are correlated with tumor growth and angiogenesis in both experimental model and human tumor. However, whether tumor growth and angiogenesis could be affected by NDRG1 in host remains unclear. This study demonstrated that NDRG1 deficiency suppressed infiltration and activation of tumor-associated macrophages in tumor. Moreover, NDRG1 deficiency specifically suppressed VEGF-induced angiogenesis in vascular endothelial cells. Thus, NDRG1 plays a critical role in tumor growth and tumor angiogenesis through tumor-associated macrophages and vascular endothelial cells.

Research Products

• [Journal Article] Tumor-derived Interleukin-1 promotes lymphangiogenesis and lymph node metastasis through M2-type macrophages (2014)
  • Author(s): Watari K, Shibata T, Kawahara A, Sata K, Nabeshima H, Shinoda A, Abe H, Azuma K, Murakami Y, Izumi, H, Takahashi T, Kage M, Kuwano M, Ono M.
  • Journal Title: PLoS ONE Volume: 9 Issue: 6 Pages: e99568-e99568
  • DOI: 10.1371/journal.pone.0099568
  • Peer Reviewed / Open Access
• [Journal Article] Tumor-derived interleukin-1 promotes lymphangiogenesis and lymph node metastasis through M2-type macrophages. (2014)
  • Author(s): Watari, K., Shibata, T., Kawahara, A., Sata, K., Nabeshima, H., Shinoda, A., Abe, H., Azuma, K., Murakami, Y., Izumi, H., Takahashi, T., Kage, M., Kuwano, M., Ono, M.
  • Journal Title: PLoS ONE Volume: 印刷中
  • Peer Reviewed
• [Journal Article] N-myc downstream-regulated gene 1 promotes tumor inflammatory angiogenesis through JNK activation and autocrine loop of interleukin-1α by human gastric cancer cells (2013)
  • Author(s): Murakami, Y., Watari, K., Ono, M, et al. 計11名
  • Journal Title: J Biol Chem Volume: 288 Issue: 35 Pages: 25025-25037
  • DOI: 10.1074/jbc.m113.472068
  • Peer Reviewed
• [Presentation] N-myc downstream regulated gene 1 (NDRG1)は血管内皮細胞のVEGF-Aシグナルに関与し、がん血管新生を制御する (2014)
  • Author(s): 篠田あい, 渡公佑, 柴田智博, 桑野信彦, 小野眞弓
  • Organizer: 第31回日本薬学会九州支部大会
  • Place of Presentation: 福岡県福岡市
  • Year and Date: 2014-12-06 – 2014-12-07
• [Presentation] N-myc downstream regulated gene 1 (NDRG1) as a novel anti-angiogenic and therapeutic target for VEGF/VEGF receptor signaling by vascular endothelial cells. (2014)
  • Author(s): Kosuke Watari, Ai Shinoda, Tomohiro Shibata, Akihiko Kawahara, Takahito Nakama, Shigeo Yoshida, Masayoshi Kage, Michihiko Kuwano, Mayumi Ono.
  • Organizer: 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics.
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2014-11-18 – 2014-11-21
• [Presentation] NDRG1 欠失変異は血管内皮細胞の機能とVEGF 依存性血管新生を特異的に抑制する (2014)
  • Author(s): 渡 公佑, 篠田 あい, 鍋島 弘嗣, 柴田 智博, 河原 明彦, 村上 雄一, 鹿毛 政義, 桑野 信彦, 小野 眞弓
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 宿主NDRG1はマクロファージの分化と成熟を制御し、がん血管新生と転移の鍵をにぎる (2014)
  • Author(s): 渡 公佑, 柴田 智博, 村上 雄一, 桑野 信彦, 小野 眞弓
  • Organizer: 第23回日本がん転移学会芸術集会・総会
  • Place of Presentation: 石川県金沢市
  • Year and Date: 2014-07-10 – 2014-07-11
• [Presentation] オクタヒドロナフタレン誘導体AMF-26はVEGF受容体の膜発現とNF-κBシグナルを阻害することによりがん血管新生を抑制する. (2014)
  • Author(s): 渡 公佑、中村 真美代、古野 綾奈、柴田 智博、村上 雄一、桑野 信彦、小野 眞弓
  • Organizer: 文科省新学術領域研究・がん支援「化学療法基盤支援活動」第3回シンポジウム
  • Place of Presentation: 沖縄県名護市
  • Year and Date: 2014-05-12
• [Presentation] Tumor-derived interleukin-1 promotes lymphangiogenesis, and lymph node metastasis through activation of M2-type macrophages by lung cancer cells. (2014)
  • Author(s): Kosuke Watari, Tomohiro Shibata, Akihiko Kawahara, Yuichi Murakami, Hiroshi Nabeshima, Ai Shinoda, Koichi Azuma, Hiroto Izumi, Masayoshi Kage, Michihiko Kuwano, Mayumi Ono.
  • Organizer: AACR Annual Meeting 2014
  • Place of Presentation: San Diego, CA
  • Year and Date: 2014-04-05 – 2014-04-09
• [Presentation] がん血管新生はN-myc downstream regulated gene-1(NDRG1)によって特異的に制御される. (2013)
  • Author(s): 渡 公佑、柴田 智博、村上 雄一、桑野 信彦、小野 眞弓
  • Organizer: 第22回日本がん転移学会学術集会・総会
  • Place of Presentation: 長野県松本市
• [Presentation] NDRG1 はマクロファージの修飾を介してがん血管新生を誘導する－NDRG1 deficiency suppresses tumor angiogenesis through interference of macrophage activation (2013)
  • Author(s): 渡 公佑、鍋島 弘嗣、福永 裕一、柴田 智博、篠田 あい、河原 明彦、村上 雄一、鹿毛 政義、桑野 信彦、小野 眞弓
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 神奈川県横浜市
• [Presentation] N-myc Downstream Regulated Gene-1(NDRG1)はマクロファージの機能化と成熟化に関与し腫瘍血管新生に影響する. (2013)
  • Author(s): 鍋島 弘嗣、渡 公佑、篠田 あい、柴田 智博、小野 眞弓
  • Organizer: 第30回日本薬学会九州支部大会
  • Place of Presentation: 長崎県佐世保市
• [Presentation] N-myc downstream regulated gene-1(NDRG1)は血管内皮細胞の機能に関与し、がん血管新生に重要な役割を果たす. (2013)
  • Author(s): 篠田 あい、渡 公佑、鍋島 弘嗣、柴田 智博、小野 眞弓
  • Organizer: 第30回日本薬学会九州支部大会
  • Place of Presentation: 長崎県佐世保市
• [Book] 血管新生・血流正常化を標的としたがん治療．最新がん薬物療法学-がん薬物療法の最新知見-． (2014)
  • Author(s): 渡公佑、小野眞弓．
  • Publisher: 日本臨牀社
• [Remarks] 九州大学大学院薬学研究院創薬腫瘍科学講座ホームページ
  • URL: http://shuyo.phar.kyushu-u.ac.jp/
• [Remarks] 九州大学大学院薬学研究院創薬腫瘍科学講座ホームページ
  • URL: http://shuyo.phar.kyushu-u.ac.jp/