Roles of nitric oxide in tumor growth.
A subclone of the human colon adenocarcinoma cell line DLD-1, which grew reproducibly as subcutaneous tumors in nude mice, was isolated. Such cells, when engineered to generate nitric oxide (NO) continuously, grew more slowly in vitro than the wild-type parental cells. This growth retardation was reversed by the addition of N-iminoethyl-L-ornithine. In nude mice, however, the tumors from these cells grew faster than those derived from wild-type cells and were markedly more vascularized, suggesting that NO may act as part of a signaling cascade for neovascularization. Recent observations that the generation of NO in human breast and gynecological cancers correlates positively with tumor grade are consistent with this hypothesis. We suggest that NO may have a dual pro- and antitumor action, depending on the local concentration of the molecule.
Jenkins
D C
DC
Wellcome Research Laboratories, Beckenham, Kent, United Kingdom.
Charles
I G
IG
Thomsen
L L
LL
Moss
D W
DW
Holmes
L S
LS
Baylis
S A
SA
Rhodes
P
P
Westmore
K
K
Emson
P C
PC
Moncada
S
S
D000230:Adenocarcinoma / Q000473:pathology*; D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002460:Cell Line; D003110:Colonic Neoplasms / Q000473:pathology*; D017931:DNA Primers; D018076:DNA, Complementary; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D008264:Macrophages; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D018076:DNA, Complementary; D015345:Oligonucleotide Probes; D011994:Recombinant Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases