A Pleiotrophin C-terminus peptide induces anti-cancer effects through RPTPβ/ζ.
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.
Diamantopoulou
Zoi
Z
Division of Genetics, Cell and Developmental Biology, Department of Biology, University of Patras, Greece.
Bermek
Oya
O
Polykratis
Apostolos
A
Hamma-Kourbali
Yamina
Y
Delbé
Jean
J
Courty
José
J
Katsoris
Panagiotis
P
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*
D002352:Carrier Proteins; D016207:Cytokines; D010446:Peptide Fragments; C066845:pleiotrophin; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5