Inverse correlation between expression of inducible nitric oxide synthase activity and production of metastasis in K-1735 murine melanoma cells.

Inverse correlation between expression of inducible nitric oxide synthase activity and production of metastasis in K-1735 murine melanoma cells.
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DOI:
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发表时间:
1994-02
期刊:
影响因子:
11.2
通讯作者:
Zhongyun Dong;A. Staroselsky;Xiaoxia Qi;Keping Xie;I. J. Fidler
Zhongyun Dong;A. Staroselsky;Xiaoxia Qi;Keping Xie;I. J. Fidler
中科院分区:
医学1区
文献类型:
--
作者:
Zhongyun Dong;A. Staroselsky;Xiaoxia Qi;Keping Xie;I. J. Fidler

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这些研究的目的是确定小鼠K-1735黑色素瘤细胞中NO合酶活性的诱导是否与其转移潜力相关。将非转移细胞、转移细胞和体细胞杂交(由非转移细胞和转移细胞融合产生)静脉注射到同源C3H/HeN小鼠中。转移细胞存活并产生实验性肺转移,而非转移细胞则没有。用肿瘤坏死因子、白细胞介素1、γ -干扰素和脂多糖联合培养各种克隆和体细胞杂交种。非转移细胞表现出高水平的诱导NO合成酶活性和NO,而转移细胞则没有。添加NO合成酶特异性抑制剂ng - monom甲基- l-精氨酸可以抑制细胞因子的细胞毒作用和NO的产生。这些数据表明,在同基因小鼠中,内源性NO的产生与K-1735细胞存活产生肺转移的能力呈负相关。
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.