Contribution of the 37-kDa laminin receptor precursor in the anti-metastatic PSP94-derived peptide PCK3145 cell surface binding

• Published in: Biochemical and biophysical research communications 2006-07, Vol.346 (1), p.358-366
• Main Authors: Annabi, Borhane, Currie, Jean-Christophe, Bouzeghrane, Mounia, Dulude, Hélène, Daigneault, Luc, Garde, Seema, Rabbani, Shafaat A., Panchal, Chandra, Wu, Jinzi J., Béliveau, Richard
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; CARBON 14; Catechin - analogs & derivatives; Catechin - pharmacology; Cell Communication; Cell Line, Tumor; COLLAGEN; Collagen Type I - pharmacology; Drug Synergism; EGCg; HORMONES; Humans; Kinetics; Laminin receptor precursor; LIGANDS; Matrix Metalloproteinase 9 - metabolism; METASTASES; Metastasis; MMP-9; Neoplasm Metastasis - drug therapy; NEOPLASMS; Oligopeptides - pharmacology; Peptide Fragments - metabolism; PEPTIDES; PRECURSOR; PROSTATE; Prostate cancer; Prostatic Secretory Proteins - metabolism; Protein Precursors - metabolism; RECEPTORS; Receptors, Cell Surface - metabolism; Receptors, Laminin - metabolism; UPTAKE
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2006.05.139

PCK3145 is an anti-metastatic synthetic peptide with promising therapeutic efficacy against hormone-refractory prostate cancer. The characterization of the PCK3145 peptide cell surface binding/internalization mechanisms and of the receptors involved remained to be explored. [ 14C]PCK3145 cell surface binding assays showed rapid and transient kinetic profile, that was inhibited by RGD peptides, laminin, hyaluronan, and type-I collagen. RGD peptides were however unable to inhibit PCK3145 intracellular uptake. Far-Western ligand binding studies enabled the identification of the 37-kDa laminin receptor precursor (37LRP) as a potential ligand for PCK3145. Overexpression of the recombinant 37LRP indeed led to an increase in PCK3145 binding but unexpectedly not to its uptake. Our data support the implication of laminin receptors in cell surface binding and in transducing PCK3145 anti-metastatic effects, and provide a rational for targeting cancers that express high levels of such laminin receptors.