2013 Fiscal Year Final Research Report
Disorder of cell adhesion system in tumor progression
| Project/Area Number |
23300351
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Yokohama City University |
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Principal Investigator |
MIYAZAKI KAORU 横浜市立大学, 付置研究所, その他 (70112068)
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| Co-Investigator(Renkei-kenkyūsha) |
HIGASHI Shouichi 横浜市立大学, 大学院・生命ナノシステム科学研究科, 准教授 (10275076)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Keywords | がん浸潤 / 細胞接着分子 / ラミニン332 / ラミニンγ2 / 上皮間葉変換（EMT） / CD44 / がん幹細胞 / 腫瘍血管 |
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| Research Abstract |
Non-invasive tumor cells are fixed on basement membranes (BMs) by stably binding to cell adhesion proteins such as laminin-332 (Lm332). However, they start to invade the BMs and then stroma during tumor progression. In this study, we investigated the mechanism of tumor invasion, mainly focusing on the interaction of tumor cells with cell adhesion proteins. Major results are as follows.
Laminin gamma2 (Lm-g2), a subunit of Lm332, is often overexpressed in invasive human cancers and hence regarded as a tumor invasion marker. We found that (1) Lm-g2 is induced in association with epithelial-mesenchymal transition of tumor cells, and (2) amino-terminal fragments of Lm-g2 directly interacts with the cancer stem cell marker CD44 in metastatic cancer cells, leading to the stimulation of their migration. These results suggest the cooperation of the two important tumor markers for cancer progression. We also found that Lm-g2 acts on vascular endothelial cells, increasing vascular permeability.
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[Journal Article] Amino-terminal fragments of laminin γ2 chain retract vascular endothelial cells and increase vascular permeability2014
Author(s)
Sato, H, Oyanagi, J., Komiya, E., Ogawa, T, Higashi, S., Miyazaki, K
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Journal Title
Cancer Sci
Volume: 105
Pages: 168-175
DOI
Peer Reviewed
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[Journal Article] Modulation of matrix metalloproteinase-9 secretion from tumor-associated macrophage-like cells by proteolytically processed laminin-332 (laminin-5)2014
Author(s)
Kamoshida, G., Ogawa, T., Oyanagi, J., Sato, H., Komiya, E., Higashi, S., Miyazaki, K., Tsuji, T
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Journal Title
Clin. Exp. Metastasis
Volume: 31
Pages: 285-291
DOI
Peer Reviewed
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[Journal Article] Angiomodulin (AGM/IGFBP-rP1), a marker of cancer vasculature, is upregulated by vascular endothelial cell growth factor and increases vascular permeability as a ligand of integrin αvβ32014
Author(s)
Komiya, E, Sato, H., Ise, I., Watanabe, N., Higashi, S., Miyagi, Y., Miyazaki, K
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Journal Title
DOI
Peer Reviewed
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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 factor2014
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: (in press)
DOI
Peer Reviewed
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[Journal Article] Elevated expression of angiomodulin (AGM/IGFBP-rP1) in tumor stroma and its roles in fibroblast activation2012
Author(s)
Komiya, E., Furuya, M., Watanabe, N., Miyagi, Y., Higashi, S., Miyazaki, K
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Journal Title
Cancer Sci
Volume: 103
Pages: 691-699
DOI
Peer Reviewed
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[Journal Article] Downregulation of a newly identified laminin, laminin-3B11, in vascular basement membranes of invasive human breast cancers2011
Author(s)
Mori, T., Kariya, Y., Komiya, T., Higashi, S., Miyagi, Y., Sekiguchi, K., Miyazaki, K
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Journal Title
Cancer Sci
Volume: 102
Pages: 1095-1100
DOI
Peer Reviewed
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[Journal Article] Structural basis for matrix metalloproteinase-2 (MMP-2)-selective inhibitory action of beta-amyloid precursor protein-derived inhibitor2011
Author(s)
Hashimoto, H., Takeuchi, T., Komatsu, K., Miyazaki, K., Sato, M., Higashi, S
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Journal Title
J. Biol. Chem
Volume: 286
Pages: 33236-33243
DOI
Peer Reviewed
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