Expression of the chemokine receptor CXCR4 and its ligand stromal cell-derived factor 1 in human brain tumors and their involvement in glial proliferation in vitro

Simone Barbero, Adriana Bajetto, Rudy Bonavia, Carola Porcile, Patrizia Piccioli, Paolo Pirani, Jean Louis Ravetti, Gianluigi Zona, Renato Spaziante, Tullio Florio, Gennaro Schettini

Research output: Contribution to journalArticle

Abstract

Chemokines are a family of proteins that chemoattract and activate cells by interacting with specific receptors on the surface of their targets. They are grouped into four classes based on the position of key cysteine residues: C, CC, CXC, and CX3C. Stromal cell-derived factor 1 (SDF1), the ligand of the CXCR4 receptor, is a CXC chemokine involved in chemotaxis and brain development that also acts as coreceptor for HIV-1 infection. It has been proposed that CXCR4 is overexpressed and required for proliferation in human brain tumor cells. We previously demonstrated that CXCR4 and SDF1 are expressed in culture of cortical type I rat astrocytes, cortical neurons, and cerebellar granule cells. In this study, we analyzed the expression of CXCR4 and SDF1 in four human brain tumor tissues, showing that CXCR4 is expressed in all tumors analyzed, whereas SDF1 is expressed only in two tumor tissues. We also investigated the possible functions of CXCR4 expressed in rat type I cortical astrocytes, demonstrating that SDF1α stimulates the proliferation of these cells in vitro. Moreover, we studied by western blot the intracellular pathway involved in cell proliferation, demonstrating that SDF1α induces the ERK1/2 phosphorylation that is reduced by the PD98059 compound, an MEK inhibitor.

Original languageEnglish
Pages (from-to)60-69
Number of pages10
JournalAnnals of the New York Academy of Sciences
Volume973
Publication statusPublished - 2002

Keywords

  • Astrocyte cell proliferation
  • CXCR4 chemokine receptor
  • Human brain tumor
  • Mitogen-activated protein kinase
  • Stromal cell-derived factor-1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Expression of the chemokine receptor CXCR4 and its ligand stromal cell-derived factor 1 in human brain tumors and their involvement in glial proliferation in vitro'. Together they form a unique fingerprint.

  • Cite this

    Barbero, S., Bajetto, A., Bonavia, R., Porcile, C., Piccioli, P., Pirani, P., Ravetti, J. L., Zona, G., Spaziante, R., Florio, T., & Schettini, G. (2002). Expression of the chemokine receptor CXCR4 and its ligand stromal cell-derived factor 1 in human brain tumors and their involvement in glial proliferation in vitro. Annals of the New York Academy of Sciences, 973, 60-69.