The cross-talk between the urokinase receptor and fMLP receptors regulates the activity of the CXCR4 chemokine receptor

Nunzia Montuori, Katia Bifulco, Maria Vincenza Carriero, Claudio La Penna, Valeria Visconte, Daniela Alfano, Ada Pesapane, Francesca Wanda Rossi, Salvatore Salzano, Guido Rossi, Pia Ragno

Research output: Contribution to journalArticlepeer-review

Abstract

The receptor (CXCR4) for the stromal-derived factor-1 (SDF1) and the urokinase-receptor (uPAR) are upregulated in various tumors. We show that CXCR4-transfected cells migrate toward SDF1 on collagen (CG) and do not on vitronectin (VN). Co-expression of cell-surface uPAR, which is a VN receptor, impairs SDF1-induced migration on CG and allows migration on VN. Blocking fMLP receptors (fMLP-R), alpha-v integrins or the uPAR region capable to interact with fMLP-Rs, impairs migration of uPAR/CXCR4-transfected cells on VN and restores their migration on CG. uPAR co-expression also reduces the adherence of CXCR4-expressing cells to various components of the extracellular matrix (ECM) and influences the partitioning of beta1 and alpha-v integrins to membrane lipid-rafts, affecting ECM-dependent signaling. uPAR interference in CXCR4 activity has been confirmed in cells from prostate carcinoma. Our results demonstrate that uPAR expression regulates the adhesive and migratory ability of CXCR4-expressing cells through a mechanism involving fMLP receptors and alpha-v integrins.

Original languageEnglish
Pages (from-to)2453-2467
Number of pages15
JournalCellular and Molecular Life Sciences
Volume68
Issue number14
DOIs
Publication statusPublished - Jul 2011

Keywords

  • CXCR4
  • fMLP receptors
  • Prostate carcinoma cells
  • uPAR
  • Urokinase-receptor

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Molecular Medicine
  • Pharmacology
  • Cellular and Molecular Neuroscience

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