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

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Abstract

The receptor (CXCR4) for the stromal-derived factor-1 (SDF1) and the urokinase-receptor (uPAR) are up-regulated 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.

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Acknowledgments

This work was supported by grants from the Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR, PRIN 2007), from Associazione Italiana per la Ricerca sul Cancro (AIRC, IG 4714) and from Ministero Italiano della Salute-FSN2007.

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Authors and Affiliations

  1. Department of Cellular and Molecular Biology and Pathology, “Federico II” University, Naples, Italy

    Nunzia Montuori, Claudio La Penna, Valeria Visconte, Ada Pesapane & Guido Rossi

  2. Department of Experimental Oncology, National Cancer Institute, Naples, Italy

    Katia Bifulco & Maria Vincenza Carriero

  3. Department of Chemistry, University of Salerno, Via Ponte don Melillo, 84084, Fisciano (Salerno), Italy

    Daniela Alfano & Pia Ragno

  4. Department of Clinical Immunology and Allergy, “Federico II” University, Naples, Italy

    Francesca Wanda Rossi

  5. Institute of Experimental Endocrinology and Oncology (National Research Council), Naples, Italy

    Salvatore Salzano

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  1. Nunzia Montuori
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  2. Katia Bifulco
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  3. Maria Vincenza Carriero
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  4. Claudio La Penna
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  5. Valeria Visconte
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  9. Salvatore Salzano
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  11. Pia Ragno
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Correspondence to Pia Ragno.

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N. Montuori and K. Bifulco contributed equally to this work.

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Montuori, N., Bifulco, K., Carriero, M.V. et al. The cross-talk between the urokinase receptor and fMLP receptors regulates the activity of the CXCR4 chemokine receptor. Cell. Mol. Life Sci. 68, 2453–2467 (2011). https://doi.org/10.1007/s00018-010-0564-7

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