ROLES OF NITRIC-OXIDE IN TUMOR-GROWTH
ROLES OF NITRIC-OXIDE IN TUMOR-GROWTH
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DOI：
10.1073/pnas.92.10.4392
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发表时间：
1995-05-09
影响因子：
11.1
通讯作者：
MONCADA, S
中科院分区：
文献类型：
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作者：
JENKINS, DC;CHARLES, IG;MONCADA, S
分离出人结肠腺癌细胞系DLD-1的亚克隆，该细胞系在裸鼠皮下可重复生长为肿瘤。当这些细胞被改造成连续产生一氧化氮（NO）时，它们在体外的生长速度比野生型亲本细胞慢。这种生长迟缓通过添加N-亚氨基乙基-L-鸟氨酸而逆转。然而，在裸鼠中，来自这些细胞的肿瘤比来自野生型细胞的肿瘤生长更快，并且明显更多地血管化，这表明NO可能作为新血管形成的信号级联的一部分。最近的观察表明，在人类乳腺癌和妇科癌症中NO的产生与肿瘤分级呈正相关，这与这一假设是一致的。我们认为，NO可能具有双重的亲和抗肿瘤作用，这取决于局部浓度的分子。
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.