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

被引:20
作者
Annabi, Borhane
Currie, Jean-Christophe
Bouzeghrane, Mounia
Dulude, Helene
Daigneault, Luc
Garde, Seema
Rabbani, Shafaat A.
Panchal, Chandra
Wu, Jinzi J.
Beliveau, Richard [1 ]
机构
[1] UQAM, Hop St Justine, Ctr Cancerol Charles Bruneau, Quebec City, PQ, Canada
[2] Univ Quebec, Dept Chim, Mol Oncol Lab, Montreal, PQ, Canada
[3] Procyon BioPharma Inc, Montreal, PQ, Canada
[4] McGill Univ, Ctr Hlth, Dept Med Physiol & Oncol, Montreal, PQ, Canada
关键词
laminin receptor precursor; prostate cancer; metastasis; MMP-9; EGCg;
D O I
10.1016/j.bbrc.2006.05.139
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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: [C-14]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. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:358 / 366
页数:9
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