Secondary stimulation from Bacillus Calmette-Guérin induced macrophages induce nitric oxide independent cell-death in bladder cancer cells

Tomas Thiel; Charlotta Ryk; Vicky Chatzakos; Katarina Hallén Grufman; Nasrin Bavand-Chobot; Jenny Flygare; N. Peter Wiklund; Petra J. De Verdier

doi:10.1016/j.canlet.2014.03.014

Secondary stimulation from Bacillus Calmette-Guérin induced macrophages induce nitric oxide independent cell-death in bladder cancer cells

Tomas Thiel, Charlotta Ryk, Vicky Chatzakos, Katarina Hallén Grufman, Nasrin Bavand-Chobot, Jenny Flygare, N. Peter Wiklund, Petra J. De Verdier

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

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.

Original language	English
Pages (from-to)	119-125
Number of pages	7
Journal	Cancer Letters
Volume	348
Issue number	1-2
DOIs	https://doi.org/10.1016/j.canlet.2014.03.014
State	Published - 2014
Externally published	Yes

Keywords

Bacillus Calmette-Guérin
Cytokines
Nitric oxide
Nitric oxide synthase
Urinary bladder cancer

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10.1016/j.canlet.2014.03.014

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title = "Secondary stimulation from Bacillus Calmette-Gu{\'e}rin induced macrophages induce nitric oxide independent cell-death in bladder cancer cells",

abstract = "The anti-tumour mechanisms following Bacillus Calmette-Gu{\'e}rin (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.",

keywords = "Bacillus Calmette-Gu{\'e}rin, Cytokines, Nitric oxide, Nitric oxide synthase, Urinary bladder cancer",

author = "Tomas Thiel and Charlotta Ryk and Vicky Chatzakos and {Hall{\'e}n Grufman}, Katarina and Nasrin Bavand-Chobot and Jenny Flygare and Wiklund, {N. Peter} and {De Verdier}, {Petra J.}",

year = "2014",

doi = "10.1016/j.canlet.2014.03.014",

language = "English",

volume = "348",

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AU - Thiel, Tomas

AU - Ryk, Charlotta

AU - Chatzakos, Vicky

AU - Hallén Grufman, Katarina

AU - Bavand-Chobot, Nasrin

AU - Flygare, Jenny

AU - Wiklund, N. Peter

AU - De Verdier, Petra J.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Bacillus Calmette-Guérin

KW - Cytokines

KW - Nitric oxide

KW - Nitric oxide synthase

KW - Urinary bladder cancer

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SP - 119

EP - 125

JO - Cancer Letters

JF - Cancer Letters

IS - 1-2

ER -

Secondary stimulation from Bacillus Calmette-Guérin induced macrophages induce nitric oxide independent cell-death in bladder cancer cells

Abstract

Keywords

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