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

OYA BERMEK; ZOI DIAMANTOPOULOU; APOSTOLIS POLYKRATIS; CÉLIA DOS SANTOS; YAMINA HAMMA-KOURBALI; FABIENNE BURLINA; JEAN DELBÉ; GÉRARD CHASSAING; DAVID G. FERNIG; PAGNAGIOTIS KATSORIS; JOSÉ COURTY

EXPERIMENTAL CELL RESEARCH

ELSEVIER INC

Lugar: Amsterdam ; Año: 2007

0014-4827

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.