期刊
JOURNAL OF IMMUNOLOGY
卷 190, 期 7, 页码 3798-3805出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1203194
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资金
- Ovarian Cancer Action
- Wellcome Trust [076256/Z/04/Z]
- Abraham Trust, Oxford, U.K.
- Medical Research Council, U.K.
- Cancer Research UK [12888, 14355] Funding Source: researchfish
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. The Journal of Immunology, 2013, 190: 3798-3805.
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