title: 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.
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 SDF1alpha stimulates the proliferation of these cells in vitro. Moreover, we studied by western blot the intracellular pathway involved in cell proliferation, demonstrating that SDF1alpha induces the ERK1/2 phosphorylation that is reduced by the PD98059 compound, an MEK inhibitor.
authors.affiliation: Service of Pharmacology and Neuroscience, Institute for Cancer Research (IST), c/o Advanced Biotechnology Center (CBA), Genoa, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Barbero
authors.forename: Adriana
authors.initials: A
authors.lastname: Bajetto
authors.forename: Rudy
authors.initials: R
authors.lastname: Bonavia
authors.forename: Corola
authors.initials: C
authors.lastname: Porcile
authors.forename: Patrizia
authors.initials: P
authors.lastname: Piccioli
authors.forename: Paolo
authors.initials: P
authors.lastname: Pirani
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Ravetti
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Zona
authors.forename: Renato
authors.initials: R
authors.lastname: Spaziante
authors.forename: Tullio
authors.initials: T
authors.lastname: Florio
authors.forename: Gennaro
authors.initials: G
authors.lastname: Schettini
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000502:physiology; D001932:Brain Neoplasms / Q000235:genetics* / Q000276:immunology; D002455:Cell Division; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009457:Neuroglia / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D013936:Thymidine