MCP-1 expression in CNS-1 astrocytoma cells: implications for macrophage infiltration into tumors in vivo.
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-beta but not other proinflammatory cytokines. However, numerous cytokines were detected in CNS-I tumors in vivo including Ltbeta, IL-1alpha, IL-1beta, TNF-alpha, TNF-beta, IL-10, and IFN-gamma. Attenuation of MCP- I 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.
Kielian
Tammy
T
Department of Pathology, Dartmouth Medical School, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA. kieliantammyl@uams.edu
van Rooijen
Nico
N
Hickey
William F
WF
D000818:Animals; D001254:Astrocytoma / Q000276:immunology* / Q000473:pathology; D001932:Brain Neoplasms / Q000276:immunology* / Q000473:pathology; D018932:Chemokine CCL2 / Q000235:genetics*; D016207:Cytokines / Q000235:genetics; D016373:DNA, Antisense / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000637:transplantation
D018932:Chemokine CCL2; D016207:Cytokines; D016373:DNA, Antisense