Inhibition of B16 melanoma metastasis by overexpression of the cysteine proteinase inhibitor cystatin C
Inhibition of B16 melanoma metastasis by overexpression of the cysteine proteinase inhibitor cystatin C
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DOI：
10.1097/00008390-199908000-00005
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发表时间：
1999-08-01
影响因子：
2.2
通讯作者：
Darmani, NA
中科院分区：
文献类型：
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作者：
Cox, JL;Sexton, PS;Darmani, NA
对于许多肿瘤类型，进展至转移与半胱氨酸蛋白酶活性增加相关。正常细胞中半胱氨酸蛋白酶调节的一种机制是通过天然蛋白酶抑制剂，半胱氨酸蛋白酶抑制剂。在这里，我们进一步表征了一个转染的细胞系，其显示出由巨细胞病毒（CMV）启动子/增强子序列驱动的胱抑素C转录增加。检查了这种半胱氨酸蛋白酶抑制剂C改变的细胞系的特性，例如体外生长、小鼠尾静脉注射后的肺定殖、半胱氨酸蛋白酶抑制剂的产生和半胱氨酸蛋白酶抑制剂活性。尽管半胱氨酸蛋白酶抑制剂转染的细胞系的生长速率与对照细胞系的生长速率之间没有差异，但转移能力存在实质性差异。与对照转染细胞系相比，未观察到半胱氨酸蛋白酶抑制剂C分泌到半胱氨酸蛋白酶抑制剂C转染细胞系的培养基中。然而，无细胞提取物中半胱氨酸蛋白酶抑制剂活性存在差异。这些结果表明，B16黑素瘤中过表达引起的半胱氨酸蛋白酶抑制剂C水平的改变改变了与转移相关的性质，（C）1999 Lippincott威廉姆斯和威尔金斯。
Progression to metastasis has been correlated with increased cysteine proteinase activity for a number of tumour types. One mechanism of cysteine proteinase regulation in normal cells is by natural protease inhibitors, the cystatins. Here we further characterize a transfected cell line showing increased cystatin C transcription driven by cytomegalovirus (CMV) promoter/enhancer sequences. Properties of this cystatin C altered cell line such as growth in vitro, lung colonization after tail vein injection in mice, production of cystatin, and cysteine proteinase inhibitor activities were examined. Although there was no difference between the growth rate of the cystatin transfected cell line and that of the control, there was a substantial difference in metastatic ability. No increase was noted in cystatin C secretion into the media for the cystatin C transfected cell line compared with the control transfected cell line. There was, however, a difference in cysteine protease inhibitor activity in the cell-free extracts, These results show that alteration of cystatin C levels by overexpression in B16 melanoma alters properties associated with metastasis, (C) 1999 Lippincott Williams & Wilkins.