NSU-MD Faculty Articles
Aberrant PGE₂ metabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells.
Publication Title
International immunopharmacology
Publisher
Elsevier Ltd
ISSN
1567-5769
Publication Date
7-1-2011
Keywords
Animals, CD11b Antigen, Carcinoma, Cell Differentiation, Cell Line, Tumor, Cell Movement, Dinoprostone, Humans, Immunosuppression, Mice, Mice, Nude, Myeloid Cells, Receptors, CXCR4, Transplantation, Heterologous, Tumor Escape, Tumor Microenvironment, Urinary Bladder Neoplasms
Abstract
Bladder cancer is associated with enhanced inflammation and characterized by deregulated prostanoid metabolism. Here we examined prostaglandin E₂ (PGE₂) 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 PGE₂. Normal bone marrow myeloid cell progenitors cultured in the presence of a bladder tumor-conditioned medium, which is enriched for PGE₂, 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 PGE₂ 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.
DOI
10.1016/j.intimp.2011.01.033
Volume
11
Issue
7
First Page
848
Last Page
855
Disciplines
Medicine and Health Sciences
NSUWorks Citation
Eruslanov, Evgeniy; Daurkin, Irina; Vieweg, Johannes; Daaka, Yehia; and Kusmartsev, Sergei, "Aberrant PGE₂ metabolism in bladder tumor microenvironment promotes immunosuppressive phenotype of tumor-infiltrating myeloid cells." (2011). NSU-MD Faculty Articles. 58.
https://nsuworks.nova.edu/hpd_md_facarticles/58
