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Mol. Cells 2010; 29(6): 617-623

Published online June 21, 2010

https://doi.org/10.1007/s10059-010-0077-0

© The Korean Society for Molecular and Cellular Biology

Soluble Epithin/PRSS14 Secreted from Cancer Cells Contains Active Angiogenic Potential

Sang Bum Kim1,4, Deokjae Lee, Joo-Won Jeong2, Chungho Kim3, Dongeun Park1, and Moon Gyo Kim*

Department of Biological Sciences, Inha University, Incheon 402-751, Korea, 1School of Biological Sciences, Seoul National University, Seoul 151-747, Korea, 2Department of Anatomy and Neurobiology, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Korea, 3Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA, 4Present address: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA

Correspondence to : *Correspondence: mgkim@inha.ac.kr

Received: March 17, 2010; Accepted: March 23, 2010

Abstract

Epithin (PRSS14/matriptase/ST14), a type II membrane protein, is involved in progression of epithelial cancers and metastasis as well as in the normal epidermal barrier function. When activated, it translocates into the cell-cell contacts and sheds into media. In order to understand the specific mechanism during tumor progression, we tested the angiogenic potential of secreted form of epithin. Epithin produced from the cancer cells shed more in hypoxia and induced motility of endothelial cells. Epithin enhanced the migration and invasion of mouse and bovine endothelial cells without cell proliferation. Furthermore, soluble epithin induced endothelial differentiation in the assay of the human endothelial microvessel-like tube formation and in that of the chicken chorioallantoic membrane. The knock-down of epithin in the 427 thymoma cell line abolished the protease activity of secreted epithin fraction, reduced the invasion of endothelial cells through matrigel, and tube formation activity. Only specific antibodies abolished the migration of endothelial cell and the vessel morphogenesis, suggesting that epithin specifically functions in these systems. Therefore, we propose that the secreted epithin in the hypoxic cancer microenvironment plays a role as a proangiogenic factor, and can be modulated with specific antibodies.

Keywords angiogenesis, epithin, hypoxia, matriptase, PRSS14

Article

Communication

Mol. Cells 2010; 29(6): 617-623

Published online June 30, 2010 https://doi.org/10.1007/s10059-010-0077-0

Copyright © The Korean Society for Molecular and Cellular Biology.

Soluble Epithin/PRSS14 Secreted from Cancer Cells Contains Active Angiogenic Potential

Sang Bum Kim1,4, Deokjae Lee, Joo-Won Jeong2, Chungho Kim3, Dongeun Park1, and Moon Gyo Kim*

Department of Biological Sciences, Inha University, Incheon 402-751, Korea, 1School of Biological Sciences, Seoul National University, Seoul 151-747, Korea, 2Department of Anatomy and Neurobiology, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Korea, 3Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA, 4Present address: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA

Correspondence to:*Correspondence: mgkim@inha.ac.kr

Received: March 17, 2010; Accepted: March 23, 2010

Abstract

Epithin (PRSS14/matriptase/ST14), a type II membrane protein, is involved in progression of epithelial cancers and metastasis as well as in the normal epidermal barrier function. When activated, it translocates into the cell-cell contacts and sheds into media. In order to understand the specific mechanism during tumor progression, we tested the angiogenic potential of secreted form of epithin. Epithin produced from the cancer cells shed more in hypoxia and induced motility of endothelial cells. Epithin enhanced the migration and invasion of mouse and bovine endothelial cells without cell proliferation. Furthermore, soluble epithin induced endothelial differentiation in the assay of the human endothelial microvessel-like tube formation and in that of the chicken chorioallantoic membrane. The knock-down of epithin in the 427 thymoma cell line abolished the protease activity of secreted epithin fraction, reduced the invasion of endothelial cells through matrigel, and tube formation activity. Only specific antibodies abolished the migration of endothelial cell and the vessel morphogenesis, suggesting that epithin specifically functions in these systems. Therefore, we propose that the secreted epithin in the hypoxic cancer microenvironment plays a role as a proangiogenic factor, and can be modulated with specific antibodies.

Keywords: angiogenesis, epithin, hypoxia, matriptase, PRSS14

Mol. Cells
Nov 30, 2023 Vol.46 No.11, pp. 655~725
COVER PICTURE
Kim et al. (pp. 710-724) demonstrated that a pathogen-derived Ralstonia pseudosolanacearum type III effector RipL delays flowering time and enhances susceptibility to bacterial infection in Arabidopsis thaliana. Shown is the RipL-expressing Arabidopsis plant, which displays general dampening of the transcriptional program during pathogen infection, grown in long-day conditions.

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