2013 Fiscal Year Final Research Report
Selective pressure driving cancer cell fate decisions: the mechanism of the creation
Project/Area Number |
23590478
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Experimental pathology
|
Research Institution | Kyoto Sangyo University |
Principal Investigator |
ITANO Naoki 京都産業大学, 総合生命科学部, 教授 (40257712)
|
Project Period (FY) |
2011 – 2013
|
Keywords | がん微小環境 / ヒアルロン酸 / がん幹細胞 / 淘汰圧 / マクロファージ |
Research Abstract |
In this study, we have investigated the mechanisms of cancer stem cell (CSC) enrichment under the selective pressure and the way in which CSCs can escape from this pressure. Flow cytometric analysis indicated the enrichment of CSC-like cells in hyaluronan synthase 2 (Has2)-overexpressing cancer cells. We also found that Has2 overexpressing cells produced significantly higher levels of TNF-alpha and TGF-beta than the control cells. Taken together, our findings provided a novel idea that CSCs can create selective pressure via the macrophage activation induced by up-regulating TNF-alpha in a hyaluronan-dependent manner. We further suggest that the anti-tumor immune action of TGF-beta allows cancer cells to escape from the selective pressure.
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[Journal Article] Crucial role of hyaluronan in neointimal formation after vascular injury2013
Author(s)
Kashima, Y., Takahashi, M., Shiba, Y., Itano, N., Izawa, A., Koyama, J., Nakayama, J., Taniguchi, S., Kimata, K., and Ikeda, U.
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Journal Title
PLoS One
Volume: 8(3)
Pages: e58760
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[Journal Article] Hyaluronan expressed by the hematopoietic microenvironment is required for bone marrow hematopoiesis2012
Author(s)
Goncharova, V., Serobyan, N., Iizuka, S., Schraufstatter, I., de Ridder, A., Povaliy, T., Wacker, V., Itano, N., Kimata, K., Orlovskaja, I.A., Yamaguchi, Y., and Khaldoyanidi, S.
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Journal Title
J. Biol. Chem
Volume: 287(30)
Pages: 25419-25433
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[Journal Article] Restriction of mast cell proliferation through hyaluronan synthesis by co-cultured fibroblasts2012
Author(s)
Takano, H., Nakazawa, S., Shirata, N., Tamba, S., Furuta, K., Tsuchiya, S., Morimoto, K., Itano, N., Irie, A., Ichikawa, A., Kimata, K., Nakayama, K., Sugimoto, Y., and Tanaka, S.
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Journal Title
Biol. Pharm. Bull
Volume: 35(3)
Pages: 408-412
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[Journal Article] Enhanced inflammation and accelerated wound closure following tetraphorbol ester application or full-thickness wounding in mice lacking hyaluronan synthases Has1 and Has32012
Author(s)
Mack, J.A., Feldman, R.J., Itano, N., Kimata, K., Lauer, M., Hascall, V.C., and Maytin, E.V.
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Journal Title
J. Invest. Dermatol
Volume: 132(1)
Pages: 198-207
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