Nitric oxide generated by iNOS reduces deformability of Lewis lung carcinoma cells
Nitric oxide generated by iNOS reduces deformability of Lewis lung carcinoma cells
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DOI：
10.1111/j.1349-7006.2004.tb03213.x
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发表时间：
2004-04-01
期刊：
影响因子：
5.7
通讯作者：
Kobayashi, H
中科院分区：
文献类型：
--
作者：
Igawa, S;Hayashi, I;Kobayashi, H
已有研究表明NO在肿瘤细胞的转移过程中起着至关重要的作用，肿瘤细胞通过诱导型一氧化氮合酶（inducible nitric oxide synthase， NOS）产生一氧化氮（NO）。由于肿瘤细胞的可变形性是控制其转移潜力的重要因素，因此本研究我们研究了NO对肿瘤细胞可变形性的调节。Lewis肺肿瘤细胞（3LL细胞）也用细胞因子混合物（il -1 β， IFNgamma和TNFalpha）孵育。采用Griess法测定上清液中亚硝酸盐/硝酸盐含量，RT-PCR法检测体外iNOS表达。细胞因子混合物产生亚硝酸盐/硝酸盐，并在细胞因子处理的细胞中表达iNOS mRNA。通过测量3LL细胞在恒定流速下通过微过滤器时产生的峰值压力来评估其变形能力。细胞因子混合物和NO供体（NOC - 18）均显著提高了滤过压力，罗丹明-phalloidin染色显示F-actin在细胞膜上聚集。综上所述，NO可降低肿瘤细胞的变形能力，提示NO是调节肿瘤转移的因素之一。
Previous studies have indicated that NO plays a crucial role in the metastasis of tumor cells and that tumor cells produce nitric oxide (NO) via inducible nitric oxide synthase (NOS). Since the deformability of tumor cells is an important factor governing their metastatic potential, in this study we investigated the regulation of tumor cell deformability by NO. Lewis lung tumor cells (3LL cells) were also incubated with a cytokine mixture (IL-1beta, IFNgamma, and TNFalpha). The nitrite/nitrate content of the supernatant was then measured by the Griess method, and iNOS expression was evaluated by RT-PCR in vitro. Nitrite/nitrate was produced in response to administration of the cytokine mixture, and iNOS mRNA was expressed in the cytokine-treated cells. The deformability of the 3LL cells was evaluated by measuring the peak pressure generated during their passage through a microfilter at a constant flow rate. Both the cytokine mixture and NO donor (NOC 18) significantly increased the filtration pressure, and the staining of the cells with rhodamine-phalloidin revealed assembly of F-actin in the cell membrane. In conclusion, NO plays a role in the decreased deformability of tumor cells, suggesting that NO is one of the factors that regulates metastasis.