Human astrocytomas and glioblastomas express monocyte chemoattractant protein-1 (MCP-1) in vivo and in vitro.
Expression of the monocyte chemoattractant protein-1 (MCP-1) was examined in human central nervous system tumours (glioblastomas and astrocytomas) and normal human brain. Northern blot analysis demonstrated constitutive expression of MCP-1 mRNA in 6 of 12 glioblastoma cell lines. Expression could be stimulated by interleukin (IL)-1 beta and tumour necrosis factor (TNF)-alpha in all cell lines tested. Immunoprecipitation demonstrated secretion of both isoforms, MCP-1 alpha and -beta, of the MCP-1 protein. Reverse-transcription polymerase chain reaction and Northern blot analysis on tissues demonstrated MCP-1 mRNA expression in 17 of 17 glioblastomas, 3 of 6 anaplastic astrocytomas and 6 of 6 low-grade astrocytomas, as well as in fetal brain but not in normal adult brain. In situ hybridization on 2 glioblastomas and 1 low-grade astrocytoma indicates that neoplastic astrocytes and endothelial cells express MCP-1 mRNA in vivo. Moreover, tumour cyst fluids of glioblastomas and astrocytomas were able to induce monocyte chemoattraction in an in vitro assay. This chemotactic activity was specifically neutralized by anti-MCP-1 antibodies in 9 of 10 samples, further demonstrating the production of bioactive MCP-1 in vivo and supporting an important role for this factor in the infiltration of monocytes/macrophages into tumour tissue.
Desbaillets
I
I
Laboratory of Tumour Biology and Genetics, University Hospital (CHUV), Lausanne, Switzerland.
Tada
M
M
de Tribolet
N
N
Diserens
A C
AC
Hamou
M F
MF
Van Meir
E G
EG
D001254:Astrocytoma / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D015152:Blotting, Northern; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism*; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012194:RNA-Directed DNA Polymerase; D014407:Tumor Cells, Cultured
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D016207:Cytokines; D012333:RNA, Messenger; D012194:RNA-Directed DNA Polymerase