Inverse correlation between expression of inducible nitric oxide synthase activity and production of metastasis in K-1735 murine melanoma cells.
The purpose of these studies was to determine whether the induction of NO synthase activity in murine K-1735 melanoma cells correlated with their metastatic potential. Nonmetastatic, metastatic, and somatic cell hybrids (produced by fusion of nonmetastatic and metastatic cells) were injected i.v. into syngeneic C3H/HeN mice. Metastatic cells survived to produce experimental lung metastases, whereas nonmetastatic cells did not. The various clones and somatic cell hybrids were incubated in vitro with combinations of tumor necrosis factor, interleukin 1, gamma-interferon, and lipopolysaccharide. Nonmetastatic cells exhibited high levels of inducible NO synthase activity and NO, whereas metastatic cells did not. Both the cytotoxic effects of the cytokines and NO production were inhibited by the addition of NG-monomethyl-L-arginine, a specific inhibitor of NO synthase. These data demonstrate an inverse correlation between production of endogenous NO and the ability of K-1735 cells to survive in syngeneic mice to produce lung metastases.
Dong
Z
Z
Department of Cell Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Staroselsky
A H
AH
Qi
X
X
Xie
K
K
Fidler
I J
IJ
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004790:Enzyme Induction; D007065:Idoxuridine / Q000493:pharmacokinetics; D007371:Interferon-gamma / Q000633:toxicity; D007375:Interleukin-1 / Q000633:toxicity; D007457:Iodine Radioisotopes; D008070:Lipopolysaccharides / Q000633:toxicity; D008546:Melanoma, Experimental / Q000201:enzymology* / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D008809:Mice, Inbred C3H; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase; D011994:Recombinant Proteins; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity
D007375:Interleukin-1; D007457:Iodine Radioisotopes; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D007065:Idoxuridine; D002118:Calcium