A48
Co-culture of ovarian cancer cells with macrophages induces expression of a Scavenger Receptor A ligand
Robin Soper1, Annette Plüddemann2, Subhankar Mukhopadhyay2, Siamon Gordon2, Frances R. Balkwill1, Thorsten Hagemann1
1Centre for Cancer and Inflammation, Institute of Cancer and the Cancer Research UK Clinical Centre, Barts and The London School of Medicine and Dentistry, London, UK, 2Sir William Dunn School of Pathology, University of Oxford, Oxford, UK
Tumour associated macrophages, TAM, have tumour-promoting activity but it is unclear how their phenotype is achieved. Here, we demonstrate that ovarian cancer cells switch co-cultured macrophages to a phenotype similar to that found in ovarian tumours. We demonstrated that in vitro co-culture of ovarian cancer cells with macrophages induces macrophage scavenger receptor A (SR-A) expression. To further validate the model we studied SR-A regulation on TAM in vitro and in vivo. In an SR-A ligand-binding assay we showed that co-culture of macrophages with tumour cells induced the expression of a SR-A ligand and led to upregulation of SR-A expression on macrophages. The expression of SR-A on macrophages is functional; whilst co-culture of wild type macrophages with tumour cells increases tumour cell invasion in a modified Boyden chamber, co-culture with macrophages from mice deficient in SR-A or competition with physiological ligands for SR-A could block invasion of tumour cells. Using ligand binding assays we evaluated targets for the SR-A receptor and their potential for blocking co-culture induced invasion. Chemical communication between tumour cells and macrophages via SR-A may be important in regulating the TAM phenotype.
