Abstract
Macrophages and monocytes migrate in response to chemotactic cytokines such as monocyte chemoattractant protein 1 (MCP-1/CCL2) in a variety of tissues including the central nervous system. Overexpression of MCP-1 has been reported in glioblastoma (GBM), which correlates to prominent macrophage infiltration characterized by this tumor type, but whether MCP-1 receptor is also expressed by the neoplastic cells remains unclear. Expression of MCP-1 and its receptor, CC chemokine receptor 2 (CCR2), were examined in GBM using cDNA microarrays and validated in two independent microarray datasets. We investigated the expression of the CCR2A isoform in human glioma cell lines and GBM, and found overexpression of CCR2A in most GBM specimens examined when compared to normal brain tissues. CCR2A is mainly localized in the cytoplasm of neoplastic cells, and pronounced neuronal cytoplasmic CCR2A immunoreactivity in tumor-infiltrating area was associated with prior chemo/radiation therapy. Glioma cells ectopically overexpressing CCR2A demonstrated increased migration compared to vector-transfected cells in vitro. Inhibition of MCP-1 synthesis suppressed migration of CCR2A-overexpressed glioma cells. Our data suggest that CCR2A might be associated with the pathobiology of GBM such as host response to treatment and tumor cell migration.
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Acknowledgements
We thank the Neurosurgery Tissue Bank at the University of California, San Francisco for contributing tissue specimens in this study. We are grateful to Sharon Reynolds for commenting on the manuscript. Funding support was provided by the Department of Neurosurgery at UCSF. UCSF is an NCI-designated Specialized Program of Research Excellence for Brain Tumors.
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Liang, Y., Bollen, A.W. & Gupta, N. CC chemokine receptor-2A is frequently overexpressed in glioblastoma. J Neurooncol 86, 153–163 (2008). https://doi.org/10.1007/s11060-007-9463-7
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DOI: https://doi.org/10.1007/s11060-007-9463-7