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MCP-1 Expression in CNS-1 Astrocytoma Cells: Implications for Macrophage Infiltration into Tumors In vivo

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Abstract

Gliomas are among the most resistant tumors to conventional anti-tumor therapy, and are typified by their highly infiltrative nature and ill-defined borders. Macrophages constitute a major proportion of the tumor cell mass in both primary human gliomas and as shown here, a CNS-1 glioma model. The objective of this study was to identify tumor-cell-derived chemotactic factor(s) which participate in macrophage recruitment into tumors in vivo. This study demonstrates the constitutive expression of monocyte chemoattractant protein-1 (MCP-1), a potent monocyte chemoattractant, by the rat astrocytoma cell line CNS-1. Characterization of cytokine expression by CNS-1 cells in vitro revealed the constitutive expression of TGF-β but not other proinflammatory cytokines. However, numerous cytokines were detected in CNS-1 tumors in vivo including Ltβ, IL-1α, IL-1β, TNF-α, TNF-β, IL-10, and IFN-γ. Attenuation of MCP-1 release from CNS-1 cells using an anti-sense approach revealed no significant alterations in macrophage infiltration into tumors in vivo, suggesting redundancy in the signal(s) involved in macrophage recruitment. Depletion of peripheral macrophages using liposome-encapsulated clodronate revealed no significant differences in tumor growth or in the degree of macrophage infiltration into CNS-1 tumors in vivo. These results indicate that CNS-1 cells produce chemotactic factors which likely participate in macrophage recruitment into tumors in vivo. Whether or not macrophage recruitment confers a growth advantage for the tumor remains to be determined.

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Authors and Affiliations

  1. Department of Pathology, Dartmouth Medical School, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA

    Tammy Kielian & William F. Hickey

  2. Department of Cell Biology and Immunology, Vrije University, Amsterdam, The Netherlands

    Nico van Rooijen

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  1. Tammy Kielian
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  2. Nico van Rooijen
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Kielian, T., van Rooijen, N. & Hickey, W.F. MCP-1 Expression in CNS-1 Astrocytoma Cells: Implications for Macrophage Infiltration into Tumors In vivo . J Neurooncol 56, 1–12 (2002). https://doi.org/10.1023/A:1014495613455

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