2008 Fiscal Year Final Research Report
MMP13 promotes prostate tumor growth in the bone microenvironment by activating TGF-β
| Project/Area Number |
19590400
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Nagoya City University |
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Principal Investigator |
FUTAKUCHI Mitsuru Nagoya City University, 大学院・医学研究科, 准教授 (60275120)
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| Co-Investigator(Renkei-kenkyūsha) |
SHIRAI Tomoyuki 名古屋市立大学, 大学院・医学研究科, 教授 (60080066)
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| Project Period (FY) |
2007 – 2008
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| Keywords | 腫瘍 / 骨転移 |
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| Research Abstract |
前立腺癌の骨転移巣では、腫瘍細胞と宿主の間質細胞である骨芽・破骨細胞が相互作用し骨転移巣が形成される。一方、MMPは腫瘍・間質相互作用で重要な役割を果たすことが知られている。本研究では、どのMMPがどのように骨微小環境での腫瘍間質相互作用に働くかを検討した。我々の開発した動物モデルを用い、ラット前立腺癌が溶骨・造骨性変化を伴い増殖する組織像が観察される骨浸潤先進部と対照として非浸潤部からRNAを抽出し、microarray解析した結果、浸潤先進部では、MMP7とMMP13が高発現していた。我々はMMP13に着目し、MMP13の免疫染色を行ったところ、ラットの骨芽細胞が陽性であった。さらにMMP13を抑制するONO4817をラットに経口投与したところ、骨浸潤先進部における活性型TGFβの濃度が減少し、破骨細胞の誘導と溶骨性変化の抑制が観察された。以上より、前立腺癌が増殖する骨微小環境では、潜在型TGFβが骨芽細胞由来のMMP13により活性化され、前立腺癌や破骨細胞にTGFβのシグナルが伝達された結果、前立腺癌の骨転移巣が進展することが考えられ、MMP13は骨微小環境での腫瘍・間質相互作用で重要な役割を果たすことが示唆された。
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[Journal Article] Transforming growth factor-beta signaling at the tumor-bone interface promotes mammary tumor growth and osteoclast activation2009
Author(s)
Futakuchi, M., Nannuru, K. C., Varney, M. L., Sadanandam, A., Nakao, K., Asai, K., Shirai, T., Sato, S. Y., and Singh, R. K.
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Journal Title
Cancer Sci 100
Pages: 71-81
Peer Reviewed
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[Journal Article] Transforming growth factor beta derived from bone matrix promotes cell proliferation of prostate cancer and osteoclast activation-associated osteolysis in the bonemicroenvironment2008
Author(s)
Sato, S., Futakuchi, M., Ogawa, K., Asamoto, M., Nakao, K., Asai, K., and Shirai, T.
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Journal Title
Cancer Sci 99
Pages: 316-223
Peer Reviewed
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[Journal Article] Differences in expression patterns of cell cycle regulators after cessation of genotoxic and non-genotoxic carcinogen treatment in the rat forestomach2008
Author(s)
Mizoguchi, Y., Ogawa, K., Futakuchi, M., Takahashi, S., Hirose, M., and Shirai, T
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Journal Title
J Toxicol Pathol 21
Pages: 77-87
Peer Reviewed
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[Journal Article] Effect of heat therapy using magnetic nanoparticles conjugated with cationic liposomes on prostate tumor in bone2008
Author(s)
Kawai, N., Futakuchi, M., Yoshida, T., Ito, A., Sato, S., Naiki, T., Honda, H., Shirai, T., and Kohri, K.
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Journal Title
Prostate 68
Pages: 784-792
Peer Reviewed
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[Journal Article] Modifying effects of chitin, chitosan and their related compounds on 2-amino-3,8-dimethylimidazo[4,5-f]qu inoxaline (MeIQx) in a rat medium-term hepatocarcinogenesis model, and their post-initiation effects in a female rat 2-stage multi-organ carcinogenesis model2008
Author(s)
Kawabe, M., Futakuchi, M., Tamano, S., Shirai, T., and Hirose, M.
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Journal Title
Food Chem Toxicol 46
Pages: 2758-2763
Peer Reviewed
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[Journal Article] Spleen but not tumor infiltration bydendritic and T cells is increased by intravenous adenovirus-Flt3 ligand injection2007
Author(s)
Solheim, J. C., Reber, A. J., Ashour, A. E., Robinson, S., Futakuchi, M., Kurz, S. G., Hood, K., Fields, R. R., Shafer, L. R., Cornell, D., Sutjipto, S., Zurawski, S., LaFace, D. M., Singh, R. K., and Talmadge, J. E.
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Journal Title
Cancer Gene Ther 14
Pages: 364-371
Peer Reviewed
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[Journal Article] Both early and late stages of hepatocarcinogenesis are enhanced in cx32 dominant negative mutant transgenic rats with disrupted gap junctional intercellular communication2007
Author(s)
Hokaiwado, N., Asamoto, M., Futakuchi, M., Ogawa, K., Takahashi, S., and Shirai, T.
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Journal Title
J Membr Biol 218
Pages: 101-106
Peer Reviewed
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[Journal Article] Combined chemopreventive effects of perilla or corn oil and indomethacin in a rat medium-term multi organ carcinogenesis model2007
Author(s)
Futakuchi, M., Hirose, M., Kawabe, M., Yamaguchi, T., Sato, S.-Y., and Shirai, T.
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Journal Title
J Toxicol Pathol 20
Pages: 245-252
Peer Reviewed
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[Presentation] Suppressive effect of COX inhibitor on osteolysis associated with prostate tumor growth in the bone microenvironment2007
Author(s)
Sato, S., Futakuchi, M., Asamoto, M., Azman, S., Naiki-Ito, A., and Shirai, T.
Organizer
66th Annual Meeting of the Japanese cancer Association
Place of Presentation
Yokohama
Year and Date
20071003-05
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[Presentation] Up-regulation of soluble RANKL at tumor-bone interface is critical for mammary tumor-induced osteolysis2007
Author(s)
Kalyan, C. N., Futakuchi, M., Wilson, T. J., Singh, R. K., Varney, L. M., Vincent, T. M., and Marcusson, E. G.
Organizer
98th Annual Meeting of American Association for Cancer Research Los Angeles
Place of Presentation
CA
Year and Date
20070414-18
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