がん血管新生及びリンパ管新生を標的にしたがん治療戦略-がんと間質の応答制御
Project/Area Number |
20015034
|
Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
|
Allocation Type | Single-year Grants |
Review Section |
Biological Sciences
|
Research Institution | Kyushu University |
Principal Investigator |
小野 眞弓 (小野 真弓) Kyushu University, 薬学研究院, 客員教授 (80128347)
|
Project Period (FY) |
2008 – 2009
|
Project Status |
Completed (Fiscal Year 2009)
|
Budget Amount *help |
¥11,000,000 (Direct Cost: ¥11,000,000)
Fiscal Year 2009: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 2008: ¥5,500,000 (Direct Cost: ¥5,500,000)
|
Keywords | がん治療 / 血管新生 / リンパ管新生 / がん間質 / 腫瘍関連マクロファージ / 骨転移 / NDRG1 / Cap43 / 炎症反応 |
Research Abstract |
がんの血管新生や浸潤本研究ではがん血管新生とリンパ管新生を標的にした新しいがん治療を創出するために、特に間質の炎症反応やマクロファージを標的にした新しいがん治療戦略研究を進めてきた。 (1) 腫瘍の悪性進展を亢進させる腫瘍関連マクロファージ(TAM)に特徴的なバイオマーカーとしてヒト胃癌症例における免疫組織染色によって、腫瘍内に浸潤してくるマクロファージ(TAM)がチミジンホスホリラーゼ(TP)を発現していることを見出した。in vitro試験において、多くの胃癌細胞株にはTPの発現は観察されなかったが、培養マクロファージは明らかにTPを発現していた。また、TP阻害剤はマクロファージの増殖を抑制しなかったが、細胞遊走を阻害した。 (2) 転移抑制遺伝子としても知られているNDRG1/Cap43ががん間質への好中球やマクロファージの集積とがん血管新生を抑制することを明らかにした。NDRG1発現膵癌細胞はgroa/CXCXI1やENA-78/CXCL5, IL-8の産生が抑制され、これにはNF-kB経路が深く関与していることを明らかにした。 (3) SGK1によるリン酸化部位を欠失させたNDRG1/Cap43の欠失変異体及びリン酸化アミノ酸点変異体を用いた検討により、NDRG1/Cap43変異体強制発現株においてはCXCケモカインの発現抑制及びNF-kB経路の抑制は認められなかった。 以上、がん間質におけるTAMの血管新生及びリンパ管新生への関与及びTAMに特異的なバイオマーカーを明らかにし、またNDRG1/Cap43によるマクロファージの誘導及び血管新生制御機構について明らかにした。本研究成果を基盤にして、TAMの物理性の高いバイオマーカーを標的にした治療薬の開発並びにNDRG1/Cap43を標的にしたがん間質治療研究をすすめ、独自性が高く有用性の高い新しいがん治療薬の研究が展開できると確信している。
|
Report
(2 results)
Research Products
(53 results)
-
[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
Related Report
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
Related Report
Peer Reviewed
-
[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
Related Report
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
Related Report
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
Related Report
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
Related Report
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
Related Report
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
Related Report
Peer Reviewed
-
[Journal Article] Overexpression of class III β -tubulin predicts good response to taxane-based chemotherapy in overian clear cell adenocarcinoma2009
Author(s)
Aoki, D., Oda, Y., Hattori, S., Taguchi, K., Ohishi, Y., Basaki, Y., Oie, S., Suzuki, N., Kono, S., Tsuneyoshi, M., Ono, M., Yanagawa, T., Kuwano, M.
-
Journal Title
Clinic. Cancer Res 15
Pages: 1473-1480
Related Report
Peer Reviewed
-
[Journal Article] Higher expression of deoxyuridinetriphosphatase(dUTPase)may predict the metastasis potential of colorectal cancer2009
Author(s)
Kawahara, A., Akagi, Y, Hattori, S., Mizobe, T., Shirouzu, K., Ono, M., Yanagawa, T., Kuwano, M., Kage, M.
-
Journal Title
J. Clinic. Pathology 62
Pages: 364-369
Related Report
Peer Reviewed
-
[Journal Article] NDRG1/Cap43 plays an essential role in tumor growth and angiogenesis suppression though the blockade of NF-κ B signaling pathway by pancreatic cancer2009
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 69
Pages: 4983-4991
Related Report
Peer Reviewed
-
[Journal Article] Ets regulates peroxiredoxinl and 5 expressions through their interaction with the high-mobility group protein B12008
Author(s)
Shiota, M., Izumi, H., Miyamoto, N., Onitsuka, T., Kashiwagi, E., Kidani, A., Hirano, G., Ono, M., Kuwano, M., Naito, S., Sasaguri, Y., and Kohno, K
-
Journal Title
Cancer Sci 99
Pages: 1950-1959
Related Report
Peer Reviewed
-
-
[Journal Article] Inhibition of bone and muscle metastases of lung cancer cells by decrease in the number of monocytes/macrophages2008
Author(s)
Hiraoka, K., Zenmyo, M., Watari, K., Iguchi, H., Fotovati, A., Kimura, Y., Hosoi, F., Shoda, T., Nagata, K., Osada, H., Ono, M., and Kuwano, M
-
Journal Title
Cancer Sci 99
Pages: 1595-1602
Related Report
Peer Reviewed
-
[Journal Article] Role of macrophages in inflammatory lymphangiogenesis : Enhanced production of vascular endothelial growth factor C and D through NF-kappaB activation2008
Author(s)
Watari, K. Nakao, S., Fotovati, A., Basaki, Y., Hosoi, F., Bereczky, B., Higuchi, R., Miyamoto. T., Kuwano., Mayumi, Ono M. Role of macroph agesa
-
Journal Title
Biochem. and Biophys. Res Commun 377
Pages: 826-831
Related Report
Peer Reviewed
-
[Journal Article] Down regulation of c-Myc and induction of an angiogenesis inhibitor, thrombospondin-1, by 5-FU in human colon cancer KM12C cells2008
Author(s)
Zhao, H., Ooyama, A., Yamamoto, M., Ikeda, R., Haraguchi, M., Tabata, S., Furukawa, T Che, X., Iwashita, K., Oka, T., Fukushima, M., Nakagawa, M., Ono, M., Kuwano, M., Akiyama, S
-
Journal Title
Cancer Lett 270
Pages: 156-163
Related Report
Peer Reviewed
-
[Journal Article] Molecular basis for the induction of an angiogenesis inhibitor, thrombospondin-1, by 5-fluorouracil2008
Author(s)
Zhao, H., Ooyama, A., Yamamoto, M., Ikeda, R., Haraguchi, M., Tabata, S., Furukawa, T., Che, X., Zhang, S., Oka, T., Fukushima, M., Nakagawa, M., Ono, M., Kuwano, M., Akiyama, S.
-
Journal Title
Cancer Res 68
Pages: 7035-7041
Related Report
Peer Reviewed
-
[Journal Article] Preclinical and clinical studies of novel breast cancer drugstargeting molecules involved in protein kinase C signaling, the putative metastasis-suppressor gene Cap43 and the Y-box binding protein-12008
Author(s)
Fujii, T., Yokoyama, G, Takahashi, H., Toh, U., Kage, M., Ono, M., Shirouzu, K., and Kuwano., M.
-
Journal Title
Current Medicinal Chem 15
Pages: 528-537
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-