CXC receptor and chemokine expression in human meningioma: SDF1/CXCR4 signaling activates ERK1/2 and stimulates meningioma cell proliferation

Federica Barbieri, Adriana Bajetto, Carola Porcile, Alessandra Pattarozzi, Alessandro Massa, Gianluigi Lunardi, Gianluigi Zona, Alessandra Dorcaratto, Jean Louis Ravetti, Renato Spaziante, Gennaro Schettini, Tullio Florio

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Recent evidence indicates that cancer cells express chemokine (CK) receptors and that their signaling is crucial for tumor proliferation, migration, and angiogenesis. The profiles of expression of CXC CK receptors (CXCR1-5) and their main ligands (growth-related oncogene, GRO1-2-3/CXCL1-2-3; interleukin 8, IL-8/CXCL8; monokine-induced γ-interferon MIG/CXCL9; γ-interferon-inducible-protein-10, IP-10/CXCL10; stromal cell-derived factor-1, SDF1/CXCL12; B-cell activating CK-1, BCA-1/CXCL13) were analyzed by reverse transcription polymerase chain reaction (RT-PCR) in surgical samples of human meningiomas. All the five receptors displayed high percentages of positive cases: 92% CXCR1, 89% CXCR2, 83% CXCR3, 78% CXCR4, and 94% CXCR5. Conversely, their ligands showed a lower pattern of expression: 40% IL-8, 42% GRO1-3, 42% IP-10, 28% MIG, 53% SDF1, and 3% BCA-1. SDF1/CXCR4 interaction plays a pivotal role in cancer proliferation. Thus, the signaling mechanisms activated by the exclusive binding between SDF1 and CXCR4 was investigated in 12 primary cultures from meningioma tissues. CXCR4 was functionally coupled as demonstrated by the significant increase of DNA synthesis in meningioma cells in response to SDF1, measured by [3H]-thymidine uptake. In three primary cultures, the SDF1-dependent mitogenic activity was associated with a marked phosphorylation of extracellular signal-regulated kinase (ERK1/2) as evaluated by Western blots. PD98059 (a MEK inhibitor) significantly reduced ERK1/2 activation, thus linking the SDF1/CXCR4 pathway to meningioma cell proliferation via ERK1/2 signal transduction. We demonstrate, for the first time in human meningiomas, the simultaneous expression of CXCR1-5 and their CKs and the mitogenic activity of SDF1/CXCR4, suggesting a pivotal role of these receptor-ligand pairs in meningeal tumors.

Original languageEnglish
Title of host publicationAnnals of the New York Academy of Sciences
Pages332-343
Number of pages12
Volume1090
DOIs
Publication statusPublished - Dec 2006

Publication series

NameAnnals of the New York Academy of Sciences
Volume1090
ISSN (Print)00778923
ISSN (Electronic)17496632

Keywords

  • Cell proliferation
  • Chemokine
  • CXCR4
  • ERK1/2
  • Meningioma
  • Primary culture
  • Receptor
  • SDF1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Barbieri, F., Bajetto, A., Porcile, C., Pattarozzi, A., Massa, A., Lunardi, G., Zona, G., Dorcaratto, A., Ravetti, J. L., Spaziante, R., Schettini, G., & Florio, T. (2006). CXC receptor and chemokine expression in human meningioma: SDF1/CXCR4 signaling activates ERK1/2 and stimulates meningioma cell proliferation. In Annals of the New York Academy of Sciences (Vol. 1090, pp. 332-343). (Annals of the New York Academy of Sciences; Vol. 1090). https://doi.org/10.1196/annals.1378.037