A Pleiotrophin C-terminus peptide induces anti-cancer effects through RPTPβ/ζ

Molecular Cancer

Research

Apostolos Polykratis¹  Zoi Diamantopoulou¹  Panagiotis Katsoris¹  Jean Delbé²  José Courty²  Yamina Hamma-Kourbali²  Oya Bermek² 

[1] Division of Genetics, Cell and Developmental Biology, Department of Biology, University of Patras, Greece;Laboratoire de recherche sur la Croissance Cellulaire, la Réparation et la Régénération Tissulaires (CRRET), CNRS UMR 7149, Université Paris XII, Avenue du Général de Gaulle, 94010, Créteil Cedex, France;

关键词: Anaplastic Lymphoma Kinase;    LNCaP Cell;    DU145 Cell;    Prostate Epithelial Cell;    Concentration Dependent Manner;   

DOI  :  10.1186/1476-4598-9-224

 received in 2010-01-29, accepted in 2010-08-25,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundPleiotrophin, also known as HARP (Heparin Affin Regulatory Peptide) is a growth factor expressed in various tissues and cell lines. Pleiotrophin participates in multiple biological actions including the induction of cellular proliferation, migration and angiogenesis, and is involved in carcinogenesis. Recently, we identified and characterized several pleiotrophin proteolytic fragments with biological activities similar or opposite to that of pleiotrophin. Here, we investigated the biological actions of P(122-131), a synthetic peptide corresponding to the carboxy terminal region of this growth factor.ResultsOur results show that P(122-131) inhibits in vitro adhesion, anchorage-independent proliferation, and migration of DU145 and LNCaP cells, which express pleiotrophin and its receptor RPTPβ/ζ. In addition, P(122-131) inhibits angiogenesis in vivo, as determined by the chicken embryo CAM assay. Investigation of the transduction mechanisms revealed that P(122-131) reduces the phosphorylation levels of Src, Pten, Fak, and Erk1/2. Finally, P(122-131) not only interacts with RPTPβ/ζ, but also interferes with other pleiotrophin receptors, as demonstrated by selective knockdown of pleiotrophin or RPTPβ/ζ expression with the RNAi technology.ConclusionsIn conclusion, our results demonstrate that P(122-131) inhibits biological activities that are related to the induction of a transformed phenotype in PCa cells, by interacing with RPTPβ/ζ and interfering with other pleiotrophin receptors. Cumulatively, these results indicate that P(122-131) may be a potential anticancer agent, and they warrant further study of this peptide.

【 授权许可】

Unknown   
© Diamantopoulou et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.