Combined cytotoxic and anti-invasive properties of redox-active nanoparticles in tumor-stroma interactions.
Tumor-stroma interaction plays an important role in tumor progression. Myofibroblasts, pivotal for tumor progression, populate the microecosystem of reactive stroma. The formation of myofibroblasts is mediated by tumor derived transforming growth factor β1 (TGFβ1) which initiates a reactive oxygen species cell type dependent expression of alpha-smooth muscle actin, a biomarker for myofibroblastic cells. Myofibroblasts express and secrete proinvasive factors significantly increasing the invasive capacity of tumor cells via paracrine mechanisms. Although antioxidants prevent myofibroblast formation, the same antioxidants increase the aggressive behavior of the tumor cells. In this study, the question was addressed of whether redox-active polymer-coated cerium oxide nanoparticles (CNP, nanoceria) affect myofibroblast formation, cell toxicity, and tumor invasion. Herein, nanoceria downregulate both the expression of alpha-smooth muscle actin positive myofibroblastic cells and the invasion of tumor cells. Furthermore, concentrations of nanoceria being non-toxic for normal (stromal) cells show a cytotoxic effect on squamous tumor cells. The treatment with redox-active CNP may form the basis for protection of stromal cells from the dominating influence of tumor cells in tumor-stroma interaction, thus being a promising strategy for chemoprevention of tumor invasion.
Institute of Biochemistry & Molecular Biology I, Medical Faculty, Heinrich-Heine-University, 40225 Duesseldorf, Germany.
Lirija
L
Alili
Maren
M
Sack
Ajay S
AS
Karakoti
Sarah
S
Teuber
Katharina
K
Puschmann
Suzanne M
SM
Hirst
Christopher M
CM
Reilly
Klaus
K
Zanger
Wilhelm
W
Stahl
Soumen
S
Das
Sudipta
S
Seal
Peter
P
Brenneisen
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002563:Cerium / Q000737:chemistry* / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D051379:Mice; D046529:Microscopy, Electron, Transmission; D058628:Myofibroblasts / Q000187:drug effects* / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
D000975:Antioxidants; D017077:Culture Media, Conditioned; D051793:Hypoxia-Inducible Factor 1; D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; D002563:Cerium; C030583:ceric oxide; D002374:Catalase; D013482:Superoxide Dismutase