title: Secondary stimulation from Bacillus Calmette-Guérin induced macrophages induce nitric oxide independent cell-death in bladder cancer cells.
abstract: The anti-tumour mechanisms following Bacillus Calmette-Guérin (BCG) treatment of bladder-cancer remain largely unknown. Previous studies have shown involvement of nitric-oxide (NO) formation in the BCG-mediated effect. We analyzed the effects of macrophage secreted factors (MSFs) from BCG-stimulated RAW264.7 cells on the bladder-cancer cell line MBT2. Direct treatment with BCG did not induce NO in MBT2-cells whereas supernatant from BCG-stimulated macrophages increased NOS2 mRNA and protein expression, NO concentrations and cell-death. Blocking NO-synthesis with the NOS-inhibitor L-NAME did not affect levels of cell-death suggesting cytotoxic pathways involving other signalling molecules than NO. Several such candidate genes were identified in a microarray.
authors.affiliation: Department of Urology, Karolinska University Hospital, Stockholm, Sweden; Urology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Thiel
authors.affiliation: Department of Urology, Karolinska University Hospital, Stockholm, Sweden; Urology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Charlotta
authors.initials: C
authors.lastname: Ryk
authors.affiliation: Department of Urology, Karolinska University Hospital, Stockholm, Sweden; Urology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Laboratory Medicine, Division of Clinical Chemistry, Karolinska Institutet and Karolinska University Hospital Huddinge, Stockholm, Sweden; Stockholm University, Department of Genetics, Microbiology and Toxicology, Stockholm, Sweden.
authors.forename: Vicky
authors.initials: V
authors.lastname: Chatzakos
authors.affiliation: Department of Urology, Karolinska University Hospital, Stockholm, Sweden; Urology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Hallén Grufman
authors.affiliation: Department of Urology, Karolinska University Hospital, Stockholm, Sweden; Urology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Nasrin
authors.initials: N
authors.lastname: Bavand-Chobot
authors.affiliation: Laboratory Medicine, Division of Clinical Chemistry, Karolinska Institutet and Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Flygare
authors.affiliation: Department of Urology, Karolinska University Hospital, Stockholm, Sweden; Urology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: N Peter
authors.initials: NP
authors.lastname: Wiklund
authors.affiliation: Department of Urology, Karolinska University Hospital, Stockholm, Sweden; Urology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. Electronic address: petra.deverdier@ki.se.
authors.forename: Petra J
authors.initials: PJ
authors.lastname: de Verdier
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D019899:Paracrine Communication / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D001500:BCG Vaccine; D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse
keywords: Bacillus Calmette-Guérin; Cytokines; Nitric oxide; Nitric oxide synthase; Urinary bladder cancer