The pattern of monocyte recruitment in tumors is modulated by MCP-1 expression and influences the rate of tumor growth.
Macrophage infiltration is an important aspect of the host response to tumor growth. Tumor-associated macrophages often exhibit intratumoral or peritumoral infiltration patterns. However, the mechanism that mediates distinctive patterns of macrophage infiltration and their impact on tumor growth is not known. We studied macrophage infiltration and the effect of this infiltration on tumor growth in mice inoculated with four human tumor cell lines. We report here that tumor cells producing high levels of monocyte chemoattractant protein-1 (MCP-1) had earlier recruitment of intratumoral macrophages than did lower producers and nonproducers. These MCP-1 high producers also had a lower tumor take rate than tumors that produced little or no MCP-1. The importance of early recruitment of monocytes was further demonstrated by introduction of fMLP (a chemotactic peptide) to the tumor sites. Administration of fMLP abolished the tumor formation when applied at the time of tumor-cell inoculation. When injection of fMLP was delayed, tumor growth was slowed but not eliminated. We also demonstrated that all MCP-1-producing tumors exhibited both intratumoral and peritumoral macrophage patterns, whereas MCP-1 nonproducers exhibited a peritumoral macrophage pattern only. The number of intratumoral macrophages was negatively correlated with tumor size. Collectively, our results suggest that (a) early recruitment of monocytes inhibits tumor growth; and (b) early intratumoral macrophage infiltration in vivo corresponds to the level of MCP-1 produced by tumors in vitro. In contrast, recruitment of neutrophils was not negatively correlated with tumor growth. Thus, early recruitment of macrophages may be beneficial to cancer patients.
Zhang
L
L
Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Massachusetts, USA.
Khayat
A
A
Cheng
H
H
Graves
D T
DT
D000818:Animals; D015152:Blotting, Northern; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009000:Monocytes / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D009504:Neutrophils / Q000502:physiology; D014407:Tumor Cells, Cultured
D018932:Chemokine CCL2; D009240:N-Formylmethionine Leucyl-Phenylalanine