Contribution of the 37-kDa laminin receptor precursor in the anti-metastatic PSP94-derived peptide PCK3145 cell surface binding
- Laboratoire d'Oncologie Moleculaire, Departement de Chimie, Universite du Quebec a Montreal, Que. (Canada)
- Centre de Cancerologie Charles-Bruneau, Hopital Sainte-Justine-UQAM, Que. (Canada)
- Procyon BioPharma, Inc., Montreal, Que. (Canada)
- Department of Medicine, Physiology, and Oncology, McGill University Health Centre, Montreal, Que. (Canada)
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: [{sup 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.
- OSTI ID:
- 20854375
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 346, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2006.05.139; PII: S0006-291X(06)01212-5; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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