37 kDa层粘连蛋白受体前体在抗转移的PSP94衍生肽PCK3145细胞表面结合中的作用。

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

作者信息

Annabi Borhane, Currie Jean-Christophe, Bouzeghrane Mounia, Dulude Hélène, Daigneault Luc, Garde Seema, Rabbani Shafaat A, Panchal Chandra, Wu Jinzi J, Béliveau Richard

机构信息

Laboratoire d'Oncologie Moléculaire, Département de Chimie, Université du Québec à Montréal, Que., Canada.

出版信息

Biochem Biophys Res Commun. 2006 Jul 21;346(1):358-66. doi: 10.1016/j.bbrc.2006.05.139. Epub 2006 Jun 2.

DOI:10.1016/j.bbrc.2006.05.139

PMID:16759641

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.

摘要

目的

PCK3145是一种抗转移合成肽，对激素难治性前列腺癌具有有前景的治疗效果。PCK3145肽的细胞表面结合/内化机制以及相关受体的特征仍有待探索。

结果

[¹⁴C]PCK3145细胞表面结合试验显示出快速且短暂的动力学特征，其受到RGD肽、层粘连蛋白、透明质酸和I型胶原的抑制。然而，RGD肽无法抑制PCK3145的细胞内摄取。Far-Western配体结合研究确定37 kDa层粘连蛋白受体前体（37LRP）为PCK3145的潜在配体。重组37LRP的过表达确实导致PCK3145结合增加，但出乎意料的是并未导致其摄取增加。