Journal
CANCER RESEARCH
Volume 65, Issue 12, Pages 5278-5283Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-04-1853
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Funding
- NCI NIH HHS [CA100324] Funding Source: Medline
- NIAMS NIH HHS [K01 AR002158] Funding Source: Medline
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Previous studies have shown that macrophages and tumor cells are comigratory in mammary tumors and that these cc types are mutually dependent for invasion. Here we show that macrophages and tumor cells are necessary and sufficient for comigration and invasion into collagen I and that this process involves a paracrine loop. Macrophages express epidermal growth factor (EGF), which promotes the formation of elongated protrusions and cell invasion by carcinoma cells. Colony stimulating factor 1 (CSF-1) produced by carcinoma cells promotes the expression of EGF by macrophages. In addition, EGF promotes the expression of CSF-1 by carcinoma cells thereby generating a positive feedback loop. Disruption of this loop by blockade of either EGF receptor or CSF-1 receptor signaling is sufficient to inhibit both macrophage and tumor cell migration and invasion.
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