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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.

SUBMITTER: Neyen C 

PROVIDER: S-EPMC3608578 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Macrophage scavenger receptor a promotes tumor progression in murine models of ovarian and pancreatic cancer.

Neyen Claudine C   Plüddemann Annette A   Mukhopadhyay Subhankar S   Maniati Eleni E   Bossard Maud M   Gordon Siamon S   Hagemann Thorsten T  

Journal of immunology (Baltimore, Md. : 1950) 20130227 7


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  ...[more]

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