Effect of HIF inhibitors on tumor hypoxia-induced dedifferentiation and metastasis of lung carcinoma cells

• Project/Area Number: 19591655
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: KOSHIKAWA Nobuko Chiba Cancer Center (Research Institute), 研究局, 研究員 (90260249)
• Co-Investigator(Kenkyū-buntansha): 竹永 啓三 千葉県がんセンター(研究所), 化学療法研究部, 研究員 (80260256)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 低酸素 / 肺癌 / 脱分化 / 転移能 / HIF阻害剤 / HIF阻害

Research Abstract

ヒト肺癌由来細胞株A549を用いて、腫瘍内低酸素状態が低酸素誘導転写因子(HIF-1およびHIF-2)を介して脱分化を誘導し、逆に幹細胞様の細胞に変化させることを見出した。
また、HIF阻害剤がこれらの変化を抑制すると共に、低酸素による実験的肺転移能の亢進を抑制すること、NOD/SCIDマウス肺同所移植実験モデルにおいて、縱隔リンパ節や腋下リンパ節への転移を抑制する傾向を示すこと見出した。

Research Products

• [Journal Article] ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis (2008)
  • Author(s): Ishikawa K, Takenaga K, Akimoto M, Koshikawa N, Yamaguchi A, Imanishi H,Nakada K, HonmaY, Hayashi J
  • Journal Title: Science 320 Pages: 661-664
  • NAID: 120007138465
• [Journal Article] Reversible re- gulation of metastasis by ROS- generating mtDNA mutations (2008)
  • Author(s): Ishikawa K, Koshikawa N, Takenaga K, Nakada K, Hayashi J
  • Journal Title: Mito- chondrion, 8 Pages: 339-344
• [Journal Article] Enhance glycolysis induced by mtDNA mutations does not regulate metastasis (2008)
  • Author(s): Ishikawa K, Hashizume O, Koshikawa N, Fukuda S, Nakada K, Takenaga K, Hayashi J
  • Journal Title: FEBS Letter 582 Pages: 3525-3530
  • NAID: 120007138501
• [Journal Article] ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis (2008)
  • Author(s): Ishikawa K, Takenaga K, Akimoto M, Koshikawa N, Yamaguchi A, Imanishi H, Nakada K, Honma Y, Hayashi J.
  • Journal Title: Science 320 Pages: 661-664
  • NAID: 120007138465
  • Peer Reviewed
• [Journal Article] Reversible regulation of metastasis by ROS-generating mtDNA mutations (2008)
  • Author(s): Ishikawa K, Koshikawa N, Takenaga K, Nakada K, Hayashi J.
  • Journal Title: Mitochondrion 8 Pages: 339-344
  • Peer Reviewed
• [Journal Article] Enhance glycolysis induced by mtDNA mutations does not regulate metastasis (2008)
  • Author(s): Ishikawa K, Hashizume O, Koshikawa N, Fukuda S, Nakada K, Takenaga K, Hayashi J.
  • Journal Title: FEBS Letter 582 Pages: 3525-3530
  • NAID: 120007138501
  • Peer Reviewed
• [Presentation] HIF-2αによる幹細胞マーカーCD133遺伝子の発現制御 (2008)
  • Author(s): 望月重信、越川信子、原口清輝、中川原章、竹永啓三
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] ROS産生を伴うミトコンドリアDNA突然変異によるヒトがん細胞の転移能の制御 (2008)
  • Author(s): 越川信子、石川香、今西秦赳、中田和人、林純一、竹永啓三
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] マウス由来細胞株および組織で発現する新規MCL-1バリアントの同定 (2008)
  • Author(s): 小嶋彰吾、百武明、越川信子、竹永啓三
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] Reversible control of metastasis by a pathogenic mtDNA mutation in ND6 (2007)
  • Author(s): Koshikawa N, Ishikawa K, Akimoto M, Yamaguchi A, Imanishi H, Nakada K, Honma Y, Hayashi J-I, Takenaga K
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] Expression of cancer stem cell-related genes in hypoxia-resistant human lung adenocarcinoma A549 cells (2007)
  • Author(s): Mochizuki S, Koshikawa N, Ohira M, Haraguchi S, Nakagawara A, Takenaga, K
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03
• [Presentation] ミトコンドリアND6遺伝子の病因性ミッセンス変異による転移能の亢進 (2007)
  • Author(s): 竹永啓三、石川 香、秋元美穂、越川信子、山口 綾、今西泰赳、中田和人、本間良夫、林 純一
  • Organizer: 第16回日本がん転移学会総会
  • Place of Presentation: 富山
  • Year and Date: 2007-07-09
• [Presentation] Expression of cancer stem cell-related genes in hypoxia-resistant human lung adenocarcinoma A549 cells. (2007)
  • Author(s): S.Mochizuki, N.Koshikawa, M.Ohira, S.Haraguchi, A.Nakagawara, K.Takenaga.
  • Organizer: 第66回日本癌学会
  • Place of Presentation: 横浜