The critical role of inflammation in angiogenesis and malignant progression by cancer cells through altered tumor microenvironment

• Project/Area Number: 19390089
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Kyushu University
• Principal Investigator: ONO Mayumi Kyushu University, 薬学研究院, 客員教授 (80128347)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2009: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2008: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2007: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: 炎症 / がん / 血管新生 / がん微小環境 / リンパ管新生 / 腫瘍関連マクロファージ / マクロファージ標的薬 / がん間質

Research Abstract

Increasing evidence confirms that chronic inflammation is the strongest link to cancer. In 1850, Rudolf Virchow from Wurzburg, Germany, was the first to link chronic inflammation with arthritis, obesity, asthma and cancer. We observed that inflammatory cytokines, IL-1β, could induce angiogenesis and lymphangiogenesis through activation of transcription factor, NF-κB and proinflammatory gene products. Enhanced angiogenesis resulted in tumor progression with macrophage infilteration and this was inhibited by macrophage targeting drugs.

Research Products

• [Journal Article] Identification of sites subjected to serine/threonine phosphorylation by SGK1 affecting N-myc downstream-regulated gene 1 (NDRG1)/Cap43-dependent suppression of angiogenic CXC chemokine expression in human pancreatic cancer cells. (2010)
  • Author(s): Murakami, Y., Hosoi, F., Izumi, H., Maruyama, Y., Ureshino, H., Watari, K., Kohno, K., Kuwano, M., Ono, M.
  • Journal Title: Biochem. and Biophys. Res Commun. (In press)
• [Journal Article] Y-box binding protein-1(YB-1)promotes cell cycle progression through CDC6-dependent pathway in human cancer cells. (2010)
  • Author(s): Basaki, Y., Taguchi, K., Izumi, H., Murakami, Y., Kubo, T., Hosoi, F., Watari, K., Nakano, K., Kawaguchi, H., Ohno, S., Kohno, K., Ono, M., Kuwano, M
  • Journal Title: Eur. J.Cancer (in press)
  • Peer Reviewed
• [Journal Article] M. The close correlation between 8-hydroxy-2'-deoxyguanosine and epidermal growth factor receptor activating mutation in non-small cell lung cancer. (2010)
  • Author(s): Kawahara, A., Azuma, K., Hattori, S., Nakashima, K., Basaki, Y., Akiba, J., Takamori, S, Aizawa, H., Yanagawa, T., Izumi, H., Kohno, K., Kono, S., Kage, M., Kuwano, M., Mayumi Ono
  • Journal Title: Human Pathol. (in press)
  • Peer Reviewed
• [Journal Article] Suppressioni of Sproutys Has a Therapeutic Effect for a Mouse Model of Ischemia by Enhancing Angiogenesis. (2009)
  • Author(s): Taniguchi, K., Sasaki, K., Watari, K., Yasukawa, H., Imaizumi, T., Ayada, T., Okamoto, F., Ishizaki, T., Kato, R., Kohno, R., Kimura, H., Sato, Y., Ono, M., Yonemitsu, Y., Yoshimura, A.
  • Journal Title: PLoS ONE. 4
• [Journal Article] N-myc downstream regulated gene 1/Cap43 suppresses tumor growth and angiogenesis of pancreatic cancer through attenuation of IKKbeta expression. (2009)
  • Author(s): Hosoi, F., Izumi, H., Kawahara, A., Yuichi, M., Kinoshita, H., Kage, M., Nishio, K., Kohno, K., Kuwano, M., Ono, M.
  • Journal Title: Cancer Res. 69 Pages: 4983-4991
• [Journal Article] M. Higher expression of deoxyuridinetriphosphatase(dUTPase)may predict the metastasis potential of colorectal cancer. (2009)
  • Author(s): Kawahara, A., Akagi, Y., Hattori, S., Mizobe, T., Shirouzu, K., Ono, M., Yanagawa, T., Kuwano, M., Kage
  • Journal Title: J.Clinic. Pathology 62 Pages: 364-369
  • Peer Reviewed
• [Journal Article] N-myc downstream regulated gene 1/Cap43 suppresses tumor growth and angiogenesis of pancreatic cancer through attenuation of IKKβ expression. (2009)
  • Author(s): Hosoi, F., Izumi, H., Kawahara, A., Yuichi, M., Kinoshita, H., Kage, M., Nishio, K., Kohno, K., Kuwano, M., Ono, M
  • Journal Title: Cancer Res. 69 Pages: 4983-4991
  • Peer Reviewed
• [Journal Article] Suppressioni of Sproutys has a therapeutic effect for a mouse model of ischemia by enhancing angiogenesis. (2009)
  • Author(s): Taniguchi, K., Sasaki, K., Watari, K., Yasukawa, H., Imaizumi, T., Ayada, T., Okamoto, F., Ishizaki, T., Kato, R., Kohno, R., Kimura, H., Sato, Y., Ono, M., Yonemitsu, Y., Yoshimura A
  • Journal Title: PLoS ONE 4
  • Peer Reviewed
• [Journal Article] Nuclear Y -box binding protein-1, a predictive marker of prognosis, is correlated with expression of HER2/ErbB2 and HER3/ErbB3 in non-small cell lung cancer. (2009)
  • Author(s): Kashihara, M., Azuma, k., Kawahara, A., Basaki, Y., Hattori, S., Yanagawa, T., Terazaki, Y., Takamori, S., Shirouzu, K., Aizawa, H., Nakao, K., Kage, M., Kuwano, M., Ono, M
  • Journal Title: Jornal of Thoracic Oncology 4 Pages: 1066-74
  • Peer Reviewed
• [Journal Article] Overexpression of Cap43 is associated with malignant status of esophageal cancer. (2009)
  • Author(s): Sohda, M., Mochida, Y., Kato, H., Miyazaki, T., Nakajima, M., Fukuchi, M., Manda, R., Fukai, Y., Masuda, N., Ono, M., Kuwano, M., Kuwano, H
  • Journal Title: Anticancer Res. 29 Pages: 965-970
  • Peer Reviewed
• [Journal Article] N-myc downstream regulated genel(NDRG1)/Cap43 may play a important role in malignant progression of prostate cancer, in its close association with E-cadherin. (2009)
  • Author(s): Song Y., Oda, Y., Hori, M., Kuroiwa, K., Ono, M., Hosoi, F., Basaki, Y., Kuwano, M., Naito, S., Tsuneyoshi, M
  • Journal Title: J.Pathol. 41 Pages: 214-222
  • Peer Reviewed
• [Journal Article] NDRG1/Cap43 play an essential role in tumor growth and angiogenesis suppression though the blockade of NF-κB signaling pathw ay by pancreatic cancer. (2009)
  • Author(s): Hosoi, H., Izumi, H., Kawahara, A., Nakashima K., Murakami, Y., Tanaka, Y., Kinoshita, H., Koga, M., Nishio, K., Kohno, K., Kuwano, M., Ono, M.
  • Journal Title: Cancer Res. (In press)
  • Peer Reviewed
• [Journal Article] Role of macrophages in inflammatory lymphangiogenesis: Enhanced production of vascular endothelial growth factor C and D through NF-κB activation. (2008)
  • Author(s): Watari, K., Nakao, S., Fotovati, A., Basaki, Y., Hosoi, F., Bereczky, B., Higuchi, R., Miyamoto, T., Kuwano, M., Ono, M.
  • Journal Title: Biochem. and Biophys. Res Commun. 377 Pages: 826-31
• [Journal Article] Review)Molecular links between tumor angiogenesis and inflammation :inflammatory stimuli of macrophages and cancer cells as targets for therapeutic strategy. (2008)
  • Author(s): Ono, M.
  • Journal Title: Cancer Sci. 99 Pages: 1501-1506
• [Journal Article] Molecular links between tumor angiogenesis and inflammation : inflam matory stimuli of macrophages and cancer cells as targets for therapeut ic strategy (2008)
  • Author(s): Ono, Mayumi
  • Journal Title: Cancer Sci. 99 Pages: 1501-1506
  • Peer Reviewed
• [Journal Article] Role of macrophages in inflammatory lymphangiogenesis : Enhanced production of vascular endothelial growth factor C and D through NF-kappaB activation. (2008)
  • Author(s): Watari, K. Nakao, S., Fotovati, A., Basaki, Y., Hosoi, F., Bereczky, B., Higuchi, R., Miyamoto. T., Kuwano., Mayumi, Ono M. Role of macrophagesa
  • Journal Title: Biochem. and Biophys. Res Commun. 377 Pages: 826-831
  • Peer Reviewed
• [Journal Article] Ets Transchption factors Regulate Peroxiredoxinl and Peroxiredoxin5 Expression through their Interaction with the High Mobility Group Prote in HMGB1 (2008)
  • Author(s): Shiota M., Izumi H., Miyamoto N., Onitsuka T., Kashiwagi E., Kidani A., Hirano G., Ono M., Kuwano M., Naito S., Sasaguri Y., Kohno K
  • Journal Title: J. Biol. Chem (in press)
  • Peer Reviewed
• [Journal Article] Inflammatory stimuli from macrophages and cancer cells synergistically promote tumor growth and angiogenesis. (2007)
  • Author(s): Kimura, Y., Watari, K., Fotovati, A., Hosoi, F., Yasumoto, K., Izumi, H., Kohno, K., Umezawa, K., Iguchi, H., Shirouzu, K., Takamori, S., Kuwano, M., Ono, M.
  • Journal Title: Cancer Sci. 98 Pages: 2009-2018
• [Journal Article] Dexamethasone inhibits IL-1・-induced corneal neovascularization: role of NF-κB-activated stromal cells in inflammatory angiogenesis. (2007)
  • Author(s): Nakao, S., Hata, Y., Miura, M., Noda, K., Kinura, Y., Kawahara, S., Kita, T., Hisatomi, T., Nakazawa, T., Jin, Y., Dana, R., Kuwano, M., Ono, M., Ishibashi, T., Hafezi-Moghadam, A.
  • Journal Title: Am. J. Path. 171 Pages: 1058-1065
• [Journal Article] Dexamethasone inhibits IL-1□-induced corneal neovascularization:role of NF-□B-activated stromal cells in inflammatory angiogenesis (2007)
  • Author(s): Nakao S., Hata Y., Miura M., Noda K., Kinura Y., Kawahara, S., Kita T., Hisatomi T., Nakazawa T., Jin Y., Dana R., Kuwano M., Ono. M., Ishibashi T., Hafezi-Moghadam A.
  • Journal Title: Am. J. Path 171 Pages: 1058-1065
  • Peer Reviewed
• [Journal Article] Inflammatory stimuli from macrophages and cancer cells synergistically promote tumor growth and angiogenesis (2007)
  • Author(s): Kimura Y., Watari K., Fotovati A., Hosoi F., Yasumoto K., Izumi H., Kohno K., Umezawa K., Iguchi H., Shirouzu K., Takamori S., Kuwano M., Ono M0
  • Journal Title: Cancer science 98 Pages: 2009-2018
  • Peer Reviewed
• [Presentation] 天然由来新規リンパ管新生阻害剤の探索 第1報. (2010)
  • Author(s): 鄭ダミ、渡公佑、白水隆喜、小野眞弓、小泉桂一、済木育夫、金ユンチュル、樋口隆一、宮本智文
  • Organizer: 日本薬学会第130回年会
  • Place of Presentation: 岡山大学島津キャンパス
• [Presentation] 炎症性サイトカイン誘導のリンパ管新生にはマクロファージ由来のVEGF-Cと-Dが関与する. (2009)
  • Author(s): 渡公佑、樋口隆一、小野眞弓、宮本智文
  • Organizer: (講演)(九大)第26回(平成21年度)日本薬学会九州支部総会・大会
  • Place of Presentation: 九大
• [Presentation] 腫瘍内に浸潤してくるマクロファージはがんの血管新生や悪性進展に重要な役割を担っている. (2009)
  • Author(s): 渡公佑、細井文仁、馬崎雄二、宮本智文、樋口隆一、小野眞弓
  • Organizer: 第3回次世代を担う若手医療薬科学シンポジウム(口演)
• [Presentation] ichihiko Kuwano N-myc downstream regulated gene 1 (NDRG1)/Cap43 suppresses tumor growth and angiogenesis of pancreatic cancer through attenuation of NF-κB signaling. (2009)
  • Author(s): Mayumi Ono, Fumihito Hosoi, Hiroto Izumi, Kazuto Nishio, Kimitoshi Kohno
  • Organizer: AACR 100th Annual Meeting 2009(ポスター)
  • Place of Presentation: Denver, Colorado, USA.
• [Presentation] N-myc downstream regulated gene 1(NDRG1)/Cap43 suppresses tumor growth and angiogenesis of pancreatic cancer through attenuation of NF-kB signaling. (2009)
  • Author(s): Mayumi Ono, Fumihito Hosoi, Hiroto Izumi, Kazuto Nishio, Kimitoshi Kohno, Michihiko Kuwano
  • Organizer: AACR 100^<th> Annual Meeting 2009(ポスター)
  • Place of Presentation: Denver, Colorado, USA.
• [Presentation] Synthesis and evaluation of 6-[(2-iminopyrrolidinyl)methyl]-5-[125I]iodouracil for mapping thymidine phosphorylase in tumors. (2009)
  • Author(s): Takahiro Mukai, Masaaki Tashiro, Masato Taketomi, Mayumi Ono, Fumihiko Yamamoto, Minoru Maeda
  • Organizer: Society of Nuclear Medicine Annual Meeting
  • Place of Presentation: Toronto, Canada
• [Presentation] がん血管新生機構と阻害剤開発. (2009)
  • Author(s): 小野眞弓
  • Organizer: 第13回日本がん分子標的治療学会学術集会(招待口演)
  • Place of Presentation: ホテルクレメント 徳島
• [Presentation] ヒト胃癌におけるN-myc Downstream-Regulated Gene-1(NDRG1)/Cap43の発現と血管新生の制御. (2009)
  • Author(s): 姥真奈美、細井文仁、村上雄一、嬉野浩樹、河原明彦、小野眞弓
  • Organizer: 第13回日本がん分子標的治療学会学術集会(口演)
  • Place of Presentation: ホテルクレメント 徳島
• [Presentation] N-myc downstream regulated gene 1(NDRG1)/Cap43による膵癌の血管新生抑制におけるNF-κBシグナルの関与. (2009)
  • Author(s): 細井文仁、和泉弘人、河原明彦、西尾和人、河野公俊、小野眞弓
  • Organizer: 第13回日本がん分子標的治療学会学術集会(口演)
  • Place of Presentation: ホテルクレメント 徳島
• [Presentation] 転移抑制遺伝子NDRG1/Cap43による膵癌の血管新生抑制におけるNF-κBシグナルの関与. (2009)
  • Author(s): 細井文仁、渡公佑、西尾和人、木下壽文、桑野信彦、小野眞弓
  • Organizer: 第18回日本がん転移学会学術集会・総会
  • Place of Presentation: 旭川グランドホテル
• [Presentation] 腫瘍の内用放射線療法および悪性度診断を目的とする、チミジンボスホリラーゼを標的とした放射性ヨウ素標識薬剤の開発. (2009)
  • Author(s): 佐野鉱平、向高弘、田代賢哲、竹富聖人、小野眞弓、前田稔
  • Organizer: 2009年度がん特定若手研究者ワークショップ
  • Place of Presentation: 蓼科(長野県)
• [Presentation] SGK1によるNDRG1-Cap43リン酸化の血管新生制御における役割. (2009)
  • Author(s): 村上雄一、細井文仁、和泉弘人、河野公俊、小野眞弓
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] N-myc downstream regulated gene 1(NDRG1)/Cap43による膵癌の血管新生抑制におけるNF-κBシグナルの関与. (2009)
  • Author(s): 細井文仁、和泉弘人、河原明彦、村上雄一、渡公佑、鹿毛政義、西尾和人、河野公俊、小野眞弓
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] YB-1によるCDC6発現を介した細胞周期の制御 (2009)
  • Author(s): 馬崎雄二、和泉弘人、田口健一、樫原正樹、渡公佑、中野賢二、河野公俊、小野眞弓、桑野信彦
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 肺癌における核内YB-1局在はgefitinib治療効果を予測するバイオマーカー. (2009)
  • Author(s): 樫原正樹、馬崎雄二、東公一、河原明彦、細井文仁、寺崎泰宏、高森信三、白水和雄、鹿毛政義、桑野信彦、小野眞弓
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] N-myc downstream regulated gene 1(NDRG1)小Cap43のヒト胃癌における腫瘍増殖と血管新生の制御 (2009)
  • Author(s): 姥真奈美、細井文仁、村上雄一、嬉野浩樹、河原明彦、鹿毛政義、小野眞弓
  • Organizer: 第3回次世代を担う若手医療薬科学シンポジウム
  • Place of Presentation: 九州大学
• [Presentation] ヒト膵癌におけるN-myc downstream regulated gene 1(NDRG1/Cap43)の機能へのSGK1によるリン酸化の関与. (2009)
  • Author(s): 村上雄一、細井文仁、姥真奈美、嬉野浩樹、和泉弘人、河野公俊、小野眞弓
  • Organizer: 第3回次世代を担う若手医療薬科学シンポジウム
  • Place of Presentation: 九州大学
• [Presentation] 腫瘍内に浸潤してくるマクロファージはがんの血管新生や悪性進展に重要な役割を担っている. (2009)
  • Author(s): 渡公佑、細井文仁、馬崎雄二、宮本智文、樋口隆一、小野眞弓
  • Organizer: 第3回次世代を担う若手医療薬科学シンポジウム
  • Place of Presentation: 九州大学
• [Presentation] ヒト膵癌におけるN-myc downstream regulated gene 1(NDRG1)/Cap43のリン酸化の役割. (2009)
  • Author(s): 村上雄一、細井文仁、姥真奈美、嬉野浩樹、和泉弘人、河野公俊、小野眞弓
  • Organizer: 第26回(平成21年度)日本薬学会九州支部総会・大会
  • Place of Presentation: 九州大学
• [Presentation] 炎症性サイトカイン誘導のリンパ管新生にはマクロファージ由来のVEGF-Cと-Dが関与する. (2009)
  • Author(s): 渡公佑、樋口隆一、小野眞弓、宮本智文
  • Organizer: 第26回(平成21年度)日本薬学会九州支部総会・大会
  • Place of Presentation: 九州大学
• [Presentation] ヒト胃癌におけるN-myc downstream regulated gene 1(NDRG1)/Cap43の機能の解析. (2009)
  • Author(s): 姥真奈美、細井文仁、村上雄一、嬉野浩樹、河原明彦、鹿毛政義、小野眞弓
  • Organizer: 第26回(平成21年度)日本薬学会九州支部総会・大会
  • Place of Presentation: 九州大学
• [Presentation] がん治療創薬の新しい標的としての血管新生と炎症 (2008)
  • Author(s): 小野眞弓
  • Organizer: 薬学研究フォーラムin東京2008
  • Place of Presentation: 東京(口頭発表)
  • Year and Date: 2008-03-14
• [Presentation] がんの血管新生とリンパ管新生におけるNF-_KBシグナルの役割. (2008)
  • Author(s): 渡公祐, 細井文仁, 村上雄一, 馬崎雄二, 宮本智文, 桑野信彦, 小野眞弓
  • Organizer: 第6 7回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] A novel therapeutic strategy of tumor angiogenesis and bone metastasis by targeting tumor-associated macrophages. (2007)
  • Author(s): Ono, M.
  • Organizer: The Sixth Japan-China Joint Conference for Cancer Research Cancer-Host Interaction
  • Place of Presentation: Hokkaido, Japan.(Invited speaker)
• [Presentation] 66th Annual Meeting of the Japanese Cancer Association (2007)
  • Author(s): Ono, M.
  • Organizer: Tumor Microenvironment ; The role of tumor-associated macrophages in malignant cancer progression
  • Place of Presentation: Yokohama, Japan.
• [Presentation] The role of tumor-associated macrophages in malignant cancer progression (2007)
  • Author(s): 小野 真弓
  • Organizer: 日本癌学会シンポジウム
  • Place of Presentation: 横浜
• [Book] 血管新生の分子メカニズムと標的分子.呼吸器内科 (2010)
  • Publisher: 科学評論社(印刷中)
• [Book] 腫瘍血管新生における炎症細胞の役割.細胞 (2008)
  • Publisher: ニューサイエンス社
• [Book] 血管新生の分子機構と標的分子(特集:肺がんの分子標的治療-最新の基礎と臨床-).呼吸器科 (2008)
  • Publisher: 科学評論社
• [Book] 血管発生・新生の分子機序マクロファージ浸潤による血管新生.医学のあゆみ (2007)
  • Publisher: 医歯薬出版
• [Book] 消化器癌浸潤・転移における間質血管新生を探る.分子消化器病4 (2007)
  • Publisher: 先端医学社
• [Remarks] ホームページ等
  • URL: http://shuyo.phar.kyushu-u.ac.jp/