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

Zoi Diamantopoulou,Jean Delbé,Oya Bermek,José Courty,Apostolos Polykratis,Panagiotis Katsoris,Yamina Hamma-Kourbali

doi:10.1186/1476-4598-9-224

Abstract

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.

Highlights

Pleiotrophin, known as HARP (Heparin Affin Regulatory Peptide) is a growth factor expressed in various tissues and cell lines
N-Syndecan and RPTPb/ζ have been implicated in neurite outgrowth [10,11], while RPTPb/ζ and Anaplastic Lymphoma Kinase (ALK) have been shown to mediate cellular migration induced by pleiotrophin as well as the mitogenic, angiogenic, and transforming activities of this growth factor [14,15,16,17,18]
We investigated the effect of these peptides on angiogenesis in vivo, using the chorioallantoic membrane (CAM) assay

Summary

Introduction

Pleiotrophin, known as HARP (Heparin Affin Regulatory Peptide) is a growth factor expressed in various tissues and cell lines. Pleiotrophin induces a transformed phenotype in several cell lines [5,6] and exhibits mitogenic, anti apoptotic, chemotactic, and angiogenic actions in vitro as well as in vivo [7,8,9,10]. N-Syndecan and RPTPb/ζ have been implicated in neurite outgrowth [10,11], while RPTPb/ζ and ALK have been shown to mediate cellular migration induced by pleiotrophin as well as the mitogenic, angiogenic, and transforming activities of this growth factor [14,15,16,17,18]. Pleiotrophin and pleiotrophin peptides modulate the biological actions of other growth factors such as VEGF, contributing to the complex mode of growth factor actions [21]

Results

Discussion

Conclusion