A basic peptide derived from the HARP C-terminus inhibits anchorage-independent growth of DU145 prostate cancer cells.

Abstract

Heparin affin regulatory peptide (HARP) is an 18 kDa heparin-binding protein that plays a key role in tumor growth. We showed previously that the synthetic peptide P(111-136) composed of the last 26 HARP amino acids inhibited HARP-induced mitogenesis. Here, to identify the exact molecular domain involved in HARP inhibition, we investigated the effect of the shorter basic peptide P(122-131) on DU145 cells, which express HARP and its receptor protein tyrosine phosphatase beta/zeta (RPTPbeta/zeta). P(122-131) was not cytotoxic; it dose-dependently inhibited anchorage-independent growth of DU145 cells. Binding studies using biotinylated P(122-131) indicated that this peptide interfered with HARP binding to DU145 cells. Investigation of the mechanisms involved suggested interference, under anchorage-independent conditions, of P(122-131) with a HARP autocrine loop in an RPTPbeta/zeta-dependent fashion. Thus, P(122-131) may hold potential for the treatment of disorders involving RPTPbeta/zeta.

• Authors: Oya Bermek, Zoi Diamantopoulou, Apostolis Polykratis, Celia Dos Santos, Yamina Hamma-Kourbali, Fabienne Burlina, Jean Delbé, Gerard Chassaing, David G Fernig, Pagnagiotis Katsoris, José Courty
• Journal: Experimental cell research (Exp Cell Res) Vol. 313 Issue 19 Pg. 4041-50 (Nov 15 2007) ISSN: 0014-4827 [Print] United States
• PMID: 17727841 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Peptide Fragments
• SMARCAL1 protein, human
• Receptor-Like Protein Tyrosine Phosphatases, Class 5
• DNA Helicases

Topics

• Cell Division (drug effects)
• Cell Line, Tumor
• DNA Helicases (physiology)
• Dose-Response Relationship, Drug
• Humans
• Male
• Peptide Fragments (pharmacology)
• Prostatic Neoplasms (drug therapy, pathology)
• Protein Binding (drug effects)
• Receptor-Like Protein Tyrosine Phosphatases, Class 5 (metabolism)