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Tsirmoula, S., Lamprou, M., Hatziapostolou, M. 
ORCID: 0000-0003-2493-7028, Kieffer, N. and Papadimitriou, E.,
2015.
Pleiotrophin-induced endothelial cell migration is regulated by xanthine oxidase-mediated generation of reactive oxygen species.
Microvascular Research, 98, pp. 74-81.
ISSN 0026-2862
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Abstract
Pleiotrophin (PTN) is a heparin-binding growth factor that induces cell migration through binding to its receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ) and integrin alpha v beta 3 (ανβ3). In the present work, we studied the effect of PTN on the generation of reactive oxygen species (ROS) in human endothelial cells and the involvement of ROS in PTN-induced cell migration. Exogenous PTN significantly increased ROS levels in a concentration and time-dependent manner in both human endothelial and prostate cancer cells, while knockdown of endogenous PTN expression in prostate cancer cells significantly down-regulated ROS production. Suppression of RPTPβ/ζ through genetic and pharmacological approaches, or inhibition of c-src kinase activity abolished PTN-induced ROS generation. A synthetic peptide that blocks PTN–ανβ3 interaction abolished PTN-induced ROS generation, suggesting that ανβ3 is also involved. The latter was confirmed in CHO cells that do not express β3 or over-express wild-type β3 or mutant β3Y773F/Y785F. PTN increased ROS generation in cells expressing wild-type β3 but not in cells not expressing or expressing mutant β3. Phosphoinositide 3-kinase (PI3K) or Erk1/2 inhibition suppressed PTN-induced ROS production, suggesting that ROS production lays down-stream of PI3K or Erk1/2 activation by PTN. Finally, ROS scavenging and xanthine oxidase inhibition completely abolished both PTN-induced ROS generation and cell migration, while NADPH oxidase inhibition had no effect. Collectively, these data suggest that xanthine oxidase-mediated ROS production is required for PTN-induced cell migration through the cell membrane functional complex of ανβ3 and RPTPβ/ζ and activation of c-src, PI3K and ERK1/2 kinases.
| Item Type: | Journal article | ||||||
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| Publication Title: | Microvascular Research | ||||||
| Creators: | Tsirmoula, S., Lamprou, M., Hatziapostolou, M., Kieffer, N. and Papadimitriou, E. | ||||||
| Publisher: | Elsevier | ||||||
| Date: | March 2015 | ||||||
| Volume: | 98 | ||||||
| ISSN: | 0026-2862 | ||||||
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| Rights: | Copyright © 2015 Elsevier Inc. All rights reserved. | ||||||
| Divisions: | Schools > School of Science and Technology | ||||||
| Record created by: | Linda Sullivan | ||||||
| Date Added: | 05 Jun 2018 07:46 | ||||||
| Last Modified: | 05 Jun 2018 07:46 | ||||||
| URI: | https://irep.ntu.ac.uk/id/eprint/33813 |
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