The role of nitric oxide in reducing deformability of Lewis lung tumor cell stimulated by inflammatory cytokines.
Highly metastatic cells, especially in the lungs, are known to be resistant to nitric oxide (NO)-mediated cytotoxicity, compared with poorly or non-metastatic cells. However, the precise mechanisms connecting NO and metastasis remain to be determined. To clarify the role of NO in the characteristic changes in NO-resistant cells in response to inflammatory cytokines, we used Lewis lung tumor (LLT) cells, which are known to be highly metastatic NO-resistant cells, and determined the changes in cell deformability and the gene expression profile after the cells were stimulated using cytokine mixture or an NO donor. Both exogenous NO and endogenous NO via inducible NO synthase produced by cytokines decreased cell deformability by enhancing actin polymerization. The expression of several genes associated with actin polymerization was changed so as to increase actin filaments in the cells by enhancing actin polymerization and by suppressing actin depolymerization, actin filament severing, and barbed-end actin filament capping. In conclusion, inflammatory cytokine stimulation reduces deformability of LLT cells and enhances actin polymerization which is mainly controlled by the same genes induced by NO.
Kokubo
Kenichi
K
Department of Medical Engineering and Technology, School of Allied Health Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan. kokubo@kitasato-u.ac.jp
Igawa
Satoshi
S
Fukuda
Ayumi
A
Shinbo
Toshihiro
T
Hirose
Minoru
M
Masuda
Noriyuki
N
Kobayashi
Hirosuke
H
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000378:metabolism* / Q000648:ultrastructure*; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D018709:Statistics, Nonparametric
D016207:Cytokines; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II