Up-regulation of CC chemokine, CCL3L1, and receptors, CCR3, CCR5 in human glioblastoma that promotes cell growth.

Human CC ligand 3-like protein 1 (CCL3L1), a member of the CC chemokine family, that induces MCP1 and RANTES, exhibits a variety of proinflammatory activities including chemotaxis, and functional and proliferative activation of leukocytes, lymphocytes and macrophages. Its signal is transmitted through transmembrane receptors, CC chemokine receptors, CCR1, CCR3 and CCR5. To examine gene expression of chemokine, CCL3L1, and its receptors, CCR1, CCR3 and CCR5, we analyzed tumor tissues from 21 patients with several types of primary gliomas. CCL3L1, CCR3 and CCR5 gene exhibited over-expression in 70% (7/10), 60% (6/10), and 60% (6/10) of glioblastoma, in comparison with lower frequencies seen in lower-grade gliomas. Transfection of CCL3L1-expression vector to glioblastoma cell line enhanced proliferation of the tumor cells. These data suggest that increased expression of the CCL3L1, CCR3 and CCR5 chemokine-receptors system is involved in brain tumorigenesis, especially in the progression of glioblastoma.