Human astrocytomas and glioblastomas express monocyte chemoattractant protein-1 (MCP-1) in vivo and in vitro.

Expression of the monocyte chemoattractant protein-I (MCP-I) was examined in human central nervous system tumours (glioblastomas and astrocytomas) and normal human brain. Northern blot analysis demonstrated constitutive expression of MCP-I mRNA in 6 of 12 glioblastoma cell lines. Expression could be stimulated by interleukin (IL)-Iα and tumour necrosis factor (TNF)-α in all cell lines tested. Immunoprecipitation demonstrated secretion of both isoforms, MCP-Iα and -β, of the MCP-I protein. Reverse-transcription polymerase chain reaction and Northern blot analysis on tissues demonstrated MCP-I 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 I low-grade astrocytoma indicates that neoplastic astrocytes and endothelial cells express MCP-I mRNA in vivo. Moreover, tumour cyst fluids of glioblastomas and astrocytoms were able to induce monocyte chemoattraction in an in vitro assay. This chemotatic activity was specifically neutralized by anti-MCP-I antibodies in 9 of samples, further demonstrating the production of bioactive MCP-I in vivo and supporting an important role for this factor in the infiltration of monocytes/macrophages into tumour tissue.