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Tight Junctions in Cancer Metastasis pp 275–289Cite as

Signaling Pathways Regulating Endothelial Cell-Cell Junctions as a Barrier to Tumor Cell Metastasis

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Part of the book series: Cancer Metastasis - Biology and Treatment ((CMBT,volume 19))

Abstract

Tumor metastasis, the spread of cancer cells from primary tumor sites to distant organs, is the main cause of mortality in cancer patients. The key steps leading to metastasis are tumor cell intravasation and extravasation, the processes by which tumor cells penetrate the junctions between endothelial cells in blood vessels and lymphatic vessels. Endothelial cell-cell junctions are organized by adherens junctions and tight junctions, and dynamically regulated by various types of extracellular stimuli to sustain vascular homeostasis and to control the transendothelial migration of inflammatory cells. Tumor cells need to weaken endothelial cell-cell junctions to successfully penetrate the endothelial barrier. Thus, transendothelial migration and metastasis of tumor cells are tightly controlled by endothelial cell-cell junctions. This article describes the molecular mechanisms that positively and negatively regulate endothelial cell-cell junctions and their impact on transendothelial migration of tumor cells and metastasis.

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Acknowledgements

We thank K. Hiratomi, W. Koeda, M. Sone, H. Yonekawa, and Y. Matsuura for technical assistance. This work was supported in part by Grants-in-Aid for Scientific Research on Innovative Areas “Fluorescence Live imaging” (No. 22113009 to S.F. and No. 22113007 to M.I.) and “Neuro-Vascular Wiring” (No. 22122003 to N.M.) of The Ministry of Education, Culture, Sports, Science, and Technology, Japan, and by grants from Japan Society for the Promotion of Science (to S.F., N.M.); the Ministry of Health, Labour, and Welfare of Japan (to N.M.); and the Program for the Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (to S.F., N.M.); Takeda Science Foundation (to M.I., N.M.); the Mitsubishi Foundation (to N.M.), Japan Cardiovascular Research Foundation (to S.F.) and AstraZeneca Research Grant (to N.M.).

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  1. Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka, 565-8565, Japan

    Shigetomo Fukuhara & Naoki Mochizuki

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  1. Shigetomo Fukuhara
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  2. Naoki Mochizuki
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Correspondence to Shigetomo Fukuhara .

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  1. Cardiff University, Institute of Cancer & Genetics, Heath Park, Cardiff, CF14 4XN, West Glamorgan, United Kingdom

    Tracey A. Martin

  2. Cardiff University, Institute of Cancer & Genetics, Heath Park, Cardiff, CF4 4XN, United Kingdom

    Wen G. Jiang

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Fukuhara, S., Mochizuki, N. (2013). Signaling Pathways Regulating Endothelial Cell-Cell Junctions as a Barrier to Tumor Cell Metastasis. In: Martin, T., Jiang, W. (eds) Tight Junctions in Cancer Metastasis. Cancer Metastasis - Biology and Treatment, vol 19. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6028-8_12

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