Contribution of the 37-kDa laminin receptor precursor in the anti-metastatic PSP94-derived peptide PCK3145 cell surface binding.
OBJECTIVE
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.
Annabi
Borhane
B
Laboratoire d'Oncologie Moléculaire, Département de Chimie, Université du Québec à Montréal, Que., Canada.
Currie
Jean-Christophe
JC
Bouzeghrane
Mounia
M
Dulude
Hélène
H
Daigneault
Luc
L
Garde
Seema
S
Rabbani
Shafaat A
SA
Panchal
Chandra
C
Wu
Jinzi J
JJ
Béliveau
Richard
R
D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D002450:Cell Communication; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D007700:Kinetics; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism*; D029584:Prostatic Secretory Proteins / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D017474:Receptors, Laminin / Q000378:metabolism*
D024042:Collagen Type I; D009842:Oligopeptides; D010446:Peptide Fragments; D029584:Prostatic Secretory Proteins; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D017474:Receptors, Laminin; C506581:tigapotide; C047981:arginyl-glycyl-aspartic acid; D002392:Catechin; C045651:epigallocatechin gallate; D020780:Matrix Metalloproteinase 9