Macrophage scavenger receptor a promotes tumor progression in murine models of ovarian and pancreatic cancer
Neyen C., Plüddemann A., Mukhopadhyay S., Maniati E., Bossard M., Gordon S., Hagemann T.
Alternatively activated macrophages express the pattern recognition receptor scavenger receptor A (SR-A).We demonstrated previously that coculture of macrophages with tumor cells upregulates macrophage SR-A expression.We show in this study that macrophage SR-A deficiency inhibits tumor cell migration in a coculture assay. We further demonstrate that coculture of tumorassociated macrophages and tumor cells induces secretion of factors that are recognized by SR-A on tumor-associated macrophages. We tentatively identified several potential ligands for the SR-A receptor in tumor cell-macrophage cocultures by mass spectrometry. Competing with the coculture-induced ligand in our invasion assay recapitulates SR-A deficiency and leads to similar inhibition of tumor cell invasion. In line with our in vitro findings, tumor progression and metastasis are inhibited in SR-A -/- mice in two in vivo models of ovarian and pancreatic cancer. Finally, treatment of tumor-bearing mice with 4F, a small peptide SR-A ligand able to compete with physiological SR-A ligands in vitro, recapitulates the inhibition of tumor progression and metastasis observed in SR-A -/- mice. Our observations suggest that SR-A may be a potential drug target in the prevention of metastatic cancer progression. Copyright © 2013 by The American Association of Immunologists, Inc.