NADPH oxidases as regulators of tumor angiogenesis: current and emerging concepts.
CONCLUSIONS
Reactive oxygen species (ROS) such as superoxide, hydrogen peroxide, and peroxynitrite are generated ubiquitously by all mammalian cells and have been understood for many decades as inflicting cell damage and as causing cancer by oxidation and nitration of macromolecules, including DNA, RNA, proteins, and lipids.


BACKGROUND
A current concept suggests that ROS can also promote cell signaling pathways triggered by growth factors and transcription factors that ultimately regulate cell proliferation, differentiation, and apoptosis, all of which are important hallmarks of tumor cell proliferation and angiogenesis. Moreover, an emerging concept indicates that ROS regulate the functions of immune cells that infiltrate the tumor environment and stimulate angiogenesis, such as macrophages and specific regulatory T cells.


RESULTS
In this article, we highlight that the NADPH oxidase family of ROS-generating enzymes are the key sources of ROS and, thus, play an important role in redox signaling within tumor, endothelial, and immune cells thereby promoting tumor angiogenesis.


CONCLUSIONS
Knowledge of these intricate ROS signaling pathways and identification of the culprit NADPH oxidases is likely to reveal novel therapeutic opportunities to prevent angiogenesis that occurs during cancer and which is responsible for the revascularization after current antiangiogenic treatment.
Centre for Cancer Research, Monash Institute of Medical Research, Monash University, Victoria, Australia.
Sanja
S
Coso
Ian
I
Harrison
Craig B
CB
Harrison
Antony
A
Vinh
Christopher G
CG
Sobey
Grant R
GR
Drummond
Elizabeth D
ED
Williams
Stavros
S
Selemidis
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D006801:Humans; D051379:Mice; D019255:NADPH Oxidases / Q000378:metabolism*; D009369:Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic; D015398:Signal Transduction
D019255:NADPH Oxidases