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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
Author(s) -
BARBERO SIMONE,
BAJETTO ADRIANA,
BONAVIA RUDY,
PORCILE CAROLA,
PICCIOLI PATRIZIA,
PIRANI PAOLO,
RAVETTI JEAN LOUIS,
ZONA GIANLUIGI,
SPAZIANTE RENATO,
FLORIO TULLIO,
SCHETTINI GENNARO
Publication year - 2002
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2002.tb04607.x
Subject(s) - cxcl14 , cxc chemokine receptors , chemokine receptor , stromal cell , microbiology and biotechnology , chemokine , xcl2 , cxcl16 , biology , chemotaxis , stromal cell derived factor 1 , cxcr4 , cell growth , cell culture , cancer research , receptor , chemistry , biochemistry , genetics
A bstract : 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.