Mechanisms for malignant tumor progression based on acquisition of 3-D invasiveness and regulation of epithelial morphogenesis
| Project/Area Number |
24300329
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Kanazawa University |
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Principal Investigator |
MATSUMOTO Kunio 金沢大学, がん進展制御研究所, 教授 (90201780)
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| Co-Investigator(Renkei-kenkyūsha) |
SAKAI Katsuya 金沢大学, がん進展制御研究所, 助教 (10523318)
NAKAMURA Takahiro 金沢大学, がん進展制御研究所, 助教 (70414018)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2013: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2012: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
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| Keywords | 細胞増殖因子 / 転移 / 薬剤耐性 / HGF / Met / 浸潤 / 人工アゴニスト / 環状ペプチド / がん細胞 / エピジェネティクス / PRC / MMP |
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| Outline of Final Research Achievements |
Tumor invasion, a typical characteristic of malignant tumors, is regulated not only by intrinsic gene expression profile but also extracellular factors. Met activation by HGF participates in tissue regeneration and tumor invasion. We here found that 1) aberrant proteasome-mediated proteolysis in PRC complex participates in activation of genes (e.g., MMP-2) involved in acquisition of 3-D invasiveness in human malignant mesothelioma cells, and 2) Met expression is regulated by hierarchal equilibrium between Met-low and Met-high populations in malignant melanoma cells, by which invasive and metastatic characteristics is conferred. Based on background for HGF-Met protein-protein interactions, Met-binding cyclic peptides were obtained by RaPID system, and the dimerized peptides induced Met activation and Met-mediated biological responses, in indistinguishable ability to HGF. Thus, we succeeded in generation of artificial Met-agonist / artificial HGF composed of macrocyclic peptide.
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Report
(4 results)
Research Products
(57 results)
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[Journal Article] Inhibition of transforming growth factor-β signaling potentiates tumor cell invasion into collagen matrix induced by fibroblast-derived hepatocyte growth factor.2014
Author(s)
Oyanagi, J., Kojima, N., Sato, H., Higashi, S., Kikuchi, K., Sakai, K., Matsumoto, K., Miyazaki, K.
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Journal Title
Exp. Cell Res.
Volume: 印刷中
Pages: 267-279
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Triple inhibition of EGFR, Met, and VEGF suppresses regrowth of HGF-triggered, erlotinib-resistant lung cancer harboring an EGFR mutation.2014
Author(s)
Nakade J, MS, Takeuchi S, Nakagawa T, Ishikawa D, MD, Sano T, PhD, Nanjo S, Yamada T, Ebi H, Zhao L, MD, Yasumoto K, Matsumoto K, Yonekura K, Yano S.
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Journal Title
J Thorcic Oncol
Volume: 印刷中
Related Report
Peer Reviewed
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[Journal Article] HGF regulates VEGF expression via the c-Met receptor downstream pathways, PI3K/Akt, MAPK and STAT3, in CT26 murine cells2013
Author(s)
Matsumura A, Kubota T, Taiyoh H, Fujiwara H, Okamoto K, Ichikawa D, Shiozaki A, Komatsu S, Nakanishi M, Kuriu Y, Murayama Y, Ikoma H, Ochiai T, Kokuba Y, Nakamura T, Matsumoto K, and Otsuji E
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Journal Title
Int J Oncol.
Volume: Vol. 42: no.2
Pages: 535-542
DOI
Related Report
Peer Reviewed
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[Journal Article] Beneficial effect of a synthetic prostacyclin agonist, ONO-1301, in rat autoimmune myocarditis model2013
Author(s)
Y. Hirata, H. Kurobe, E. Uematsu, S. Yagi, T. Soeki, H. Yamada, D. Fukuda, M. Shimabukuro, M. Nakayama, K. Matsumoto, Y. Sakai, T. Kitagawa, M. Sata
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Journal Title
Eur J Pharmacol.
Volume: 699
Pages: 81-87
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Interruption of the HGF paracrine loop by NK4, an HGF antagonist, reduces VEGF expression of CT26 cells.2013
Author(s)
Kubota T, Matsumura A, Taiyoh H, Izumiya Y, Fujiwara H, Okamoto K, Ichikawa D, Shiozaki A, Komatsu S, Nakanishi M, Kuriu Y, Murayama Y, Ikoma H, Ochiai T, Nakamura T, Matsumoto K, Nakamura T, Otsuji E.
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Journal Title
Oncol Report
Volume: 30
Pages: 567-572
DOI
Related Report
Peer Reviewed
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[Journal Article] Lower gefitinib dose led to earlier resistance acquisition before emergence of T790M mutation in epidermal growth factor receptor-mutated lung cancer model.2013
Author(s)
Hayakawa H, Ichihara E, Ohashi K, Ninomiya T, Yasugi M, Takata S, Sakai K, Matsumoto K, Takigawa N, Tanimoto M, Kiura K.
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Journal Title
Cancer Sci
Volume: 104
Pages: 1440-1446
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] A synthetic prostacyclin agonist thrombozane synthase inhibitory activity, ONO-1301, protects myocardium from ischemia/reperfusion injury.2012
Author(s)
Hirata Y, Shimabukuro M, Uematsu E, Soeki T, Yamada H, Sakai Y, Nakamura M, Matsumoto K, Igarashi T, Sata M
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Journal Title
European Journal of Pharmacology
Volume: 674
Pages: 352-358
DOI
Related Report
Peer Reviewed
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[Journal Article] E7050, a Met kinase inhibitor, reverses three different mechanisms of hepatocyte growth factor-induced resistance to tyrosine kinase inhibitors in EGFR mutant lung cancer cells2012
Author(s)
Wang W, Li Q, Takeuchi S, Yamada T, Koizumi H, Nakamura T, Matsumoto K, Mukaida N, Nishioka Y, Sone S, Uenaka T, Yano S
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Journal Title
Clin Cancer Res.
Volume: 18
Pages: 1663-1671
DOI
Related Report
Peer Reviewed
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[Journal Article] Dual inhibition of met kinase and angiogenesis to overcome HGF-induced EGFR-TKI resistance in EGFR mutant lung cancer2012
Author(s)
Takeuchi S, Wang W, Li Q, Yamada T, Kita K, Donev IS, Nakamura T, Matsumoto K, Shimizu E, Nishioka Y, Sone S, Nakagawa T, Uenaka T, Yano
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Journal Title
The American Journal of Pathology
Volume: 181
Pages: 1034-1043
DOI
Related Report
Peer Reviewed
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