Nitric oxide (NO) may be an important mediator of tumour angiogenesis and metastasis formation. Tumour cell derived NO may be important in the regulation of angiogenesis and vasodilatation of the blood vessels surrounding a tumour. The aims of the present study were, firstly, to determine whether malignant melanoma cells and normal melanocytes had nitric oxide synthase (NOS) activity (measured by the conversion of L-arginine to L-citrulline) and, secondly, to determine whether there was a difference in NOS activity between malignant and normal cell types. This paper assays NOS activity directly in lysates from normal human melanocyte and malignant melanoma cell lines. The enzyme activity was not inducible with bacterial lipopolysaccharide and could be heat denatured. The activity of NOS was demonstrated to be both NADPH-and calcium-dependent and it was inhibitable in a dosedependent manner by the NOS inhibitorNw-nitro-L-argi-nine methyl ester. We conclude that melanoma and melanocyte cells express a constitutive form of NOS. Finally, nitric oxide synthase activity in melanoma cell lines was found to be significantly greater than in normal melanocytes. These findings suggest that NO synthesis is elevated in malignant melanoma. An elevated NO concentration in melanoma is expected to promote metastases by maintaining a vasodilator tone in the blood vessels in and around the melanoma.
展开▼
机译：一氧化氮 （NO） 可能是肿瘤血管生成和转移形成的重要介质。肿瘤细胞来源的 NO 可能在调节肿瘤周围血管的血管生成和血管舒张中很重要。本研究的目的是，首先，确定恶性黑色素瘤细胞和正常黑色素细胞是否具有一氧化氮合酶 （NOS） 活性（通过 L-精氨酸转化为 L-瓜氨酸来测量），其次，确定恶性和正常细胞类型之间的 NOS 活性是否存在差异。本文直接测定了正常人黑色素细胞和恶性黑色素瘤细胞系裂解物中的NOS活性。细菌脂多糖不能诱导酶活性，可热变性。NOS的活性被证明是NADPH和钙依赖性的，并且NOS抑制剂Nw-硝基-L-精氨酸-九甲酯以剂量依赖性方式抑制。我们得出结论，黑色素瘤和黑色素细胞表达组成型 NOS。最后，发现黑色素瘤细胞系中的一氧化氮合酶活性明显高于正常黑色素细胞。这些发现表明，恶性黑色素瘤的 NO 合成升高。黑色素瘤中 NO 浓度升高预计会通过维持黑色素瘤内部和周围血管中的血管扩张剂张力来促进转移。
展开▼
