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

Abstract

PURPOSE:

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.

RESULTS:

[(14)C]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.

CONCLUSIONS:

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.

• Authors: Borhane Annabi, Jean-Christophe Currie, Mounia Bouzeghrane, Hélène Dulude, Luc Daigneault, Seema Garde, Shafaat A Rabbani, Chandra Panchal, Jinzi J Wu, Richard Béliveau
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 346 Issue 1 Pg. 358-66 (Jul 21 2006) ISSN: 0006-291X [Print] United States
• PMID: 16759641 (Publication Type: Journal Article)

Chemical References

• Collagen Type I
• Oligopeptides
• Peptide Fragments
• Prostatic Secretory Proteins
• Protein Precursors
• Receptors, Cell Surface
• Receptors, Laminin
• tigapotide
• arginyl-glycyl-aspartic acid
• Catechin
• epigallocatechin gallate
• Matrix Metalloproteinase 9

Topics

• Catechin (analogs & derivatives, pharmacology)
• Cell Communication
• Cell Line, Tumor
• Collagen Type I (pharmacology)
• Drug Synergism
• Humans
• Kinetics
• Matrix Metalloproteinase 9 (metabolism)
• Neoplasm Metastasis (drug therapy)
• Oligopeptides (pharmacology)
• Peptide Fragments (metabolism)
• Prostatic Secretory Proteins (metabolism)
• Protein Precursors (metabolism)
• Receptors, Cell Surface (metabolism)
• Receptors, Laminin (metabolism)