title: A Pleiotrophin C-terminus peptide induces anti-cancer effects through RPTPβ/ζ.
abstract: BACKGROUND
  Pleiotrophin, 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.
  
  
  RESULTS
  Our 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.
  
  
  CONCLUSIONS
  In 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.
authors.affiliation: Division of Genetics, Cell and Developmental Biology, Department of Biology, University of Patras, Greece.
authors.forename: Zoi
authors.initials: Z
authors.lastname: Diamantopoulou
authors.forename: Oya
authors.initials: O
authors.lastname: Bermek
authors.forename: Apostolos
authors.initials: A
authors.lastname: Polykratis
authors.forename: Yamina
authors.initials: Y
authors.lastname: Hamma-Kourbali
authors.forename: Jean
authors.initials: J
authors.lastname: Delbé
authors.forename: José
authors.initials: J
authors.lastname: Courty
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Katsoris
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000737:chemistry*; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology*; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D010446:Peptide Fragments; C066845:pleiotrophin; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5