35 research outputs found
Dynamin2- and endothelial nitric oxide synthaseāregulated invasion of bladder epithelial cells by uropathogenic Escherichia coli
eNOS-mediated S-nitrosylation of dynamin2 promotes infection of epithelial cells by E. coli
Aberrant PGEā metabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells.
Bladder cancer is associated with enhanced inflammation and characterized by deregulated prostanoid metabolism. Here we examined prostaglandin Eā (PGEā) metabolism and myeloid cell subsets that infiltrate tumor tissue using two xenograft models of human bladder cancer. Human bladder tumor xenografts implanted into athymic nude mice become highly infiltrated with host CD11b myeloid cells of bone marrow origin. Fast growing SW780 bladder tumor xenografts were infiltrated with heterogeneous CD11b myeloid cell subsets including tumor-associated macrophages and myeloid-derived suppressor cells. In contrast, majority of myeloid cells in tumor tissue from slow growing bladder cancer Urothel 11 displayed more immature, homogenous phenotype and comprised mostly MHC II class-negative myeloid-derived suppressor cells. We demonstrate that human bladder tumors secrete substantial amounts of PGEā. Normal bone marrow myeloid cell progenitors cultured in the presence of a bladder tumor-conditioned medium, which is enriched for PGEā, failed to differentiate into mature APCs and acquired phenotype of the myeloid-derived suppressor cells or inflammatory macrophages with up-regulated chemokine receptor CXCR4. Collectively our data demonstrate that enhanced cancer-related inflammation and deregulated PGEā metabolism in tumor microenvironment promote immunosuppressive pro-tumoral phenotype of myeloid cells in bladder cancer. These data also suggest that not only local tumor microenvironment but other factors such as stage of cancer disease and pace of tumor growth could markedly influence the phenotype, differentiation and immune function of myeloid cells in tumor tissue