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[Cancer Research 65, 5278-5283, June 15, 2005]
© 2005 American Association for Cancer Research

Experimental Therapeutics, Molecular Targets, and Chemical Biology

Macrophages Promote the Invasion of Breast Carcinoma Cells via a Colony-Stimulating Factor-1/Epidermal Growth Factor Paracrine Loop

Sumanta Goswami1, Erik Sahai1,4, Jeffrey B. Wyckoff1, Michael Cammer3, Dianne Cox1, Fiona J. Pixley2, E. Richard Stanley2, Jeffrey E. Segall1 and John S. Condeelis1,3

Departments of 1 Anatomy and Structural Biology, 2 Developmental and Molecular Biology, 3 Analytical Imaging Facility, Albert Einstein College of Medicine, Bronx, New York and 4 Tumour Cell Biology Laboratory, Cancer Research UK London Research Institute, London, United Kingdom

Requests for reprints: Sumanta Goswami, Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461. Phone: 718-430-4453; Fax: 718-430-8996; E-mail: sgoswami{at}aecom.yu.edu.

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.




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Copyright © 2005 by the American Association for Cancer Research.