A basic peptide derived from the HARP C-terminus inhibits anchorage-independent growth of DU145 prostate cancer cells.
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.
Bermek
Oya
O
Laboratoire de recherche sur la Croissance Cellulaire, la Réparation et la Régénération Tissulaires (CRRET), CNRS UMR 7149, Université Paris 12, 61 Avenue du Général de Gaulle, 94010 Créteil Cedex, France.
Diamantopoulou
Zoi
Z
Polykratis
Apostolis
A
Dos Santos
Celia
C
Hamma-Kourbali
Yamina
Y
Burlina
Fabienne
F
Delbé
Jean
J
Chassaing
Gerard
G
Fernig
David G
DG
Katsoris
Pagnagiotis
P
Courty
José
J
D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004265:DNA Helicases / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011485:Protein Binding / Q000187:drug effects; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000378:metabolism
D010446:Peptide Fragments; C412482:SMARCAL1 protein, human; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D004265:DNA Helicases