Impact of inducible nitric oxide synthase gene on tumor progression
Impact of inducible nitric oxide synthase gene on tumor progression
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DOI：
10.1097/cej.0b013e3282f75f29
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发表时间：
2009-02-01
影响因子：
2.4
通讯作者：
Esumi, Hiroyasu
中科院分区：
文献类型：
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作者：
Tatemichi, Masayuki;Ogura, Tsutomu;Esumi, Hiroyasu
我们研究了诱导型一氧化氮合酶（iNOS）基因在肿瘤促进和进展中的作用。在第一项研究中，在皮下注射苯并（a）芘到iNOS缺陷型（iNOS（-/-））和野生型（iNOS（+/+））小鼠中1周后，将异物（塑料板）皮下插入致癌物注射部位以诱发慢性炎症。在第二项研究中，从第一项研究中诱导的肿瘤中制备具有不同NOS基因状态的原代培养肿瘤细胞（PCTc），并将其植入iNOS（+/+）和iNOS（-/-）小鼠的皮下间隙中，制成四种不同的NOS基因状态组合。尽管经受塑料板诱导的炎症[p-IN（+）]的小鼠表现出比P-IN（-）的小鼠显著更短的肿瘤潜伏期，但NOS基因状态在p-IN（-）或p-IN（+）组中对其没有影响。iNOS（+/+）p-IN（+）小鼠的显微侵袭率和基质金属蛋白酶mRNA表达水平均高于iNOS（-/-）p-IN（+）小鼠。在第二项研究中，仅在将NOS基因导入iNOS（+/+）小鼠的情况下，在皮下植入的肿瘤中也观察到显微侵袭，尽管PCTc或宿主小鼠中的NOS基因状态不影响肿瘤生长曲线。这些数据表明，NOS基因与肿瘤进展，而不是肿瘤发生，在这个实验模型。间质细胞和癌细胞中的NOS基因在侵袭中起重要作用。抑制NOS基因活性可能有助于炎症相关癌症的局部癌症控制。欧洲癌症预防杂志1-8：1-8（C）2009年沃尔特斯·克鲁沃健康垂直酒吧利平科特威廉姆斯&威尔金斯。
We investigated the involvement of the inducible nitric oxide synthase (iNOS) gene in tumor promotion and progression. In the first study, 1 week after subcutaneous injection of benzo(a)pyrene into iNOS-deficient (iNOS(-/-)) and wild-type (iNOS(+/+)) mice, a foreign body (plastic plate) was subcutaneously inserted into the carcinogen injection site to evoke chronic inflammation. In the second study, primarily cultured tumor cells (PCTc) with different NOS gene status were prepared from tumors induced in the first study, and they were implanted into the subcutaneous space of iNOS(+/+) and iNOS(-/-) mice, making four different combinations of NOS gene status. Although the mice that were subjected to plastic plate-induced inflammation [p-IN(+)] exhibited significantly shorter tumor latency than those with P-IN(-), NOS gene status did not affect it in the p-IN(-) or p-IN(+) groups. The rate of microscopic invasion and expression levels of matrix metalloproteinase mRNA were, however, higher in iNOS(+/+) p-IN(+) than iNOS(-/-) p-IN(+) mice. In the second study, microscopic invasion was also observed in the subcutaneously implanted tumors only in the case of PCTc with NOS gene into iNOS(+/+) mice, although NOS gene status in PCTc or host mice did not affect the tumor growth curve. These data suggest that the NOS gene was associated with tumor progression, rather than tumorigenesis, in this experimental model. The NOS gene in both the stromal and cancer cells played an important role in invasion. Inhibition of NOS gene activity might be useful for local cancer control in inflammation-associated cancers. European Journal of Cancer Prevention 18:1-8 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.