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.
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.
Barbero
Simone
S
Service of Pharmacology and Neuroscience, Institute for Cancer Research (IST), c/o Advanced Biotechnology Center (CBA), Genoa, Italy.
Bajetto
Adriana
A
Bonavia
Rudy
R
Porcile
Corola
C
Piccioli
Patrizia
P
Pirani
Paolo
P
Ravetti
Jean Louis
JL
Zona
Gianluigi
G
Spaziante
Renato
R
Florio
Tullio
T
Schettini
Gennaro
G
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
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