Macrophages promote the invasion of breast carcinoma cells via a colony-stimulating factor-1/epidermal growth factor paracrine loop.
Previous studies have shown that macrophages and tumor cells are comigratory in mammary tumors and that these cell 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.
Goswami
Sumanta
S
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. sgoswami@aicom.yu.edu
Sahai
Erik
E
Wyckoff
Jeffrey B
JB
Cammer
Michael
M
Cox
Dianne
D
Pixley
Fiona J
FJ
Stanley
E Richard
ER
Segall
Jeffrey E
JE
Condeelis
John S
JS
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D018920:Coculture Techniques; D004815:Epidermal Growth Factor / Q000096:biosynthesis / Q000502:physiology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D025461:Feedback, Physiological; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors
D004815:Epidermal Growth Factor; D016173:Macrophage Colony-Stimulating Factor; D066246:ErbB Receptors; D016186:Receptor, Macrophage Colony-Stimulating Factor