title: The role of inflammation in bladder cancer.
abstract: The aim of this book chapter is to present the latest basic research developments on the role of inflammation in bladder cancer and provide insights into their future clinical significance in preventing bladder carcinogenesis and progression. Bladder cancer is a highly immunogenic malignancy. Urothelial cancer cells aim to manipulate the immune system by inhibiting its cytotoxic function while stimulating the secretion of growth promoting factors. Cytokine-induced imbalances in the distribution and differentiation of tumor-infiltrating cytotoxic cells can boost bladder cancer cell proliferation. Tumor-induced release of excessive amount of cytokines causes an "inflammatory storm" which drives metastasis formation via degradation of extracellular matrix proteins. Tumor-related selective cyclooxygenase-2 (COX-2) upregulation suppresses the cell-mediated immune response via aberrant prostaglandin metabolism resulting in failure of differentiation of myeloid cell progenitors into mature antigen-presenting cells. T cells are capable of increasing the oxidative stress on bladder cancer cells via induction of COX-2 and STEAP expression. Some evidence also suggests that COX-2 activation may be also involved in inflammation-mediated cancer stem cell proliferation. Antibodies against the VEGF-co-receptor neuropilin decrease the angiogenetic potential of bladder cancer cells. Inflammation-based predictive bladder cancer models have demonstrated to accurately predict response to treatment both in the curative and palliative setting. While randomized trials do not support a clinical benefit for the use of anti-inflammatory drugs (i.e., celecoxib, atorvastatin) in preventing recurrence of low-grade bladder cancer, further investigations are warranted in the setting of high-grade tumors since the immune response to cancer stimuli is most probably more pronounced in advanced stages.
authors.affiliation: Department of Urology, University Hospital Tübingen, Eberhard-Karls University, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany, georgios.gakis@googlemail.com.
authors.forename: Georgios
authors.initials: G
authors.lastname: Gakis
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control
chemical_list: D000893:Anti-Inflammatory Agents