CXCR4 Activation Induces Epidermal Growth Factor Receptor Transactivation in an Ovarian Cancer Cell Line

Authors

  • CAROLA PORCILE,

    1. Pharmacology and Neuroscience, National Institute for Cancer Research c/o Centro Biotecnologie Avanzate, Genoa, Italy
    2. Section of Pharmacology, Department of Oncology, Biology, and Genetics, University of Genoa, Genoa, Italy
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  • ADRIANA BAJETTO,

    1. Section of Pharmacology, Department of Oncology, Biology, and Genetics, University of Genoa, Genoa, Italy
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  • SIMONE BARBERO,

    1. Pharmacology and Neuroscience, National Institute for Cancer Research c/o Centro Biotecnologie Avanzate, Genoa, Italy
    2. Section of Pharmacology, Department of Oncology, Biology, and Genetics, University of Genoa, Genoa, Italy
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  • PAOLO PIRANI,

    1. Pharmacology and Neuroscience, National Institute for Cancer Research c/o Centro Biotecnologie Avanzate, Genoa, Italy
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  • GENNARO SCHETTINI

    Corresponding author
    1. Pharmacology and Neuroscience, National Institute for Cancer Research c/o Centro Biotecnologie Avanzate, Genoa, Italy
    2. Section of Pharmacology, Department of Oncology, Biology, and Genetics, University of Genoa, Genoa, Italy
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Address for correspondence: Gennaro Schettini, Service of Pharmacology and Neuroscience, IST c/o CBA Largo Rosanna Benzi, 10-16132 Genoa, Italy. Voice: +39-10-5737254; fax: +39-10-5737257. e-mail: schettini@cba.unige.it

Abstract

Abstract: Chemokines are a family of proteins that have pleiotropic biological effects. They are well known to regulate the recruitment and trafficking of leukocytes to sites of inflammation. Chemokines are grouped into four classes based on the positions of key cysteine residues: C, CC, CXC, and CX3C. Stromal cell-derived factor-1 (SDF-1), the ligand of the CXCR4 receptor, is a CXC chemokine and is a highly conserved gene. Ovarian cancer typically disseminates widely in the abdomen, a characteristic that limits curative therapy. The mechanisms that promote ovarian cancer proliferation are incompletely understood. We studied a human ovarian adenocarcinoma cell line (OC 314) and investigated the role of CXCR4 activation by SDF-1 in human ovarian cancer. We demonstrate that CXCR4 and SDF-1 mRNA are expressed in OC 314. We show that SDF-1α induces proliferation in ovarian cancer cells in a dose-dependent manner. Moreover, we demonstrate that the SDF-1-dependent proliferation correlates to the phosphorylation and activation of extracellular signal-regulated kinases (ERK)1/2, which in turn are correlated to epidermal growth factor (EGF) receptor transactivation. In fact, AG1478, a specific inhibitor of the EGF receptor kinase, blocked both SDF-1α-dependent proliferation and ERK1/2 activation.

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