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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\u2013macrophage 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\u2212\/\u2212 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\u2212\/\u2212 mice. Our observations suggest that SR-A may be a potential drug target in the prevention of metastatic cancer progression.<\/jats:p>","DOI":"10.4049\/jimmunol.1203194","type":"journal-article","created":{"date-parts":[[2013,2,28]],"date-time":"2013-02-28T15:18:25Z","timestamp":1362064705000},"page":"3798-3805","source":"Crossref","is-referenced-by-count":114,"title":["Macrophage Scavenger Receptor A Promotes Tumor Progression in Murine Models of Ovarian and Pancreatic Cancer"],"prefix":"10.1093","volume":"190","author":[{"given":"Claudine","family":"Neyen","sequence":"first","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford , Oxford OX1 3RE,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Pl\u00fcddemann","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford , Oxford OX1 3RE,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhankar","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford , Oxford OX1 3RE,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Maniati","sequence":"additional","affiliation":[{"name":"Centre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London , London EC1M 6BQ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maud","family":"Bossard","sequence":"additional","affiliation":[{"name":"Centre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London , London EC1M 6BQ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siamon","family":"Gordon","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford , Oxford OX1 3RE,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Hagemann","sequence":"additional","affiliation":[{"name":"Centre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London , London EC1M 6BQ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,4,1]]},"reference":[{"key":"2025032406495487800_r1","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nature07205","article-title":"Cancer-related inflammation","volume":"454","author":"Mantovani","year":"2008","journal-title":"Nature"},{"key":"2025032406495487800_r2","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.cell.2010.03.014","article-title":"Macrophage diversity enhances tumor progression and metastasis","volume":"141","author":"Qian","year":"2010","journal-title":"Cell"},{"key":"2025032406495487800_r3","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nri978","article-title":"Alternative activation of macrophages","volume":"3","author":"Gordon","year":"2003","journal-title":"Nat. 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