title: Macrophage scavenger receptor a promotes tumor progression in murine models of ovarian and pancreatic cancer.
abstract: 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 tumor-associated 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.
authors: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
authors: Claudine
authors: C
authors: Neyen
authors: Annette
authors: A
authors: Plüddemann
authors: Subhankar
authors: S
authors: Mukhopadhyay
authors: Eleni
authors: E
authors: Maniati
authors: Maud
authors: M
authors: Bossard
authors: Siamon
authors: S
authors: Gordon
authors: Thorsten
authors: T
authors: Hagemann
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008024:Ligands; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009361:Neoplasm Invasiveness / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000071228:Polyelectrolytes; D011108:Polymers / Q000378:metabolism; D011485:Protein Binding; D051117:Scavenger Receptors, Class A / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D000071228:Polyelectrolytes; D011108:Polymers; D051117:Scavenger Receptors, Class A