Macrophage Scavenger Receptor A Promotes Tumor Progression in Murine Models of Ovarian and Pancreatic Cancer
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- Claudine Neyen
- *Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom; and
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- Annette Plüddemann
- *Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom; and
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- Subhankar Mukhopadhyay
- *Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom; and
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- Eleni Maniati
- †Centre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, United Kingdom
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- Maud Bossard
- †Centre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, United Kingdom
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- Siamon Gordon
- *Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom; and
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- Thorsten Hagemann
- †Centre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, United Kingdom
説明
<jats:title>Abstract</jats:title> <jats:p>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.</jats:p>
収録刊行物
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- The Journal of Immunology
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The Journal of Immunology 190 (7), 3798-3805, 2013-04-01
The American Association of Immunologists