MCP-1 expression in CNS-1 astrocytoma cells: Implications for macrophage infiltration into tumors in vivo

T. Kielian, N. Van Rooijen, W. F. Hickey

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalJournal of Neuro-Oncology
Volume56
Issue number1
DOIs
StatePublished - 2002

Keywords

  • Astrocytoma
  • MCP-1
  • Macrophages
  • TGF-β

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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