Expression of CXC chemokine receptors 1-5 and their ligands in human glioma tissues: role of CXCR4 and SDF1 in glioma cell proliferation and migration.
Chemokines have been involved in cellular processes associated to malignant transformation such as proliferation, migration and angiogenesis. The expression of five CXC chemokine receptors and their main ligands was analysed by RT-PCR in 31 human astrocytic neoplasms. The mRNAs for all the receptors analysed were identified in a high percentage of tumours, while their ligands showed lower expression. CXCR4 and SDF1 were the most frequently mRNA identified (29/31 and 13/31 of the gliomas studied, respectively). Thus, we further analysed the cell localization of CXCR4 and SDF1 in immunohistochemistry experiments. We show a marked co-localization of CXCR4 and SDF1 in tumour cells, mainly evident in psudolpalisade and microcystic degeneration areas and in the vascular endothelium. In addition, hSDF1alpha induced a significant increase of DNA synthesis in primary human glioblastoma cell cultures and chemotaxis in a glioblastoma cell line. These results provide evidence of the expression of multiple CXC chemokines and their receptors in brain tumours and that in particular CXCR4 and SDF1 sustain proliferation and migration of glioma cells to promote malignant progression.
Bajetto
Adriana
A
Department of Oncology, Biology and Genetics, University of Genova, Viale Benedetto XV, 2, 16132 Genova, Italy. adriana.bajetto@unige.it <adriana.bajetto@unige.it>
Barbieri
Federica
F
Dorcaratto
Alessandra
A
Barbero
Simone
S
Daga
Antonio
A
Porcile
Carola
C
Ravetti
Jean Louis
JL
Zona
Gianluigi
G
Spaziante
Renato
R
Corte
Giorgio
G
Schettini
Gennaro
G
Florio
Tullio
T
D001483:Base Sequence; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D019743:Chemokines, CXC / Q000378:metabolism / Q000502:physiology*; D017931:DNA Primers; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D019707:Receptors, Chemokine / Q000378:metabolism* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019743:Chemokines, CXC; D017931:DNA Primers; D008024:Ligands; D019707:Receptors, Chemokine