Jenkinson S R, Barraclough R, West C R, Rudland P S
Molecular Medicine Group, School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, UK.
Br J Cancer. 2004 Jan 12;90(1):253-62. doi: 10.1038/sj.bjc.6601483.
Elevated levels of the calcium-binding protein S100A4 are associated with poor patient survival in breast cancer patients and induce metastasis in rodent models. To investigate the effects of S100A4 on different components of the metastatic process, epithelial cells lines have been isolated from nonmalignant tumours in neu transgenic mice and from malignant tumours in neu/S100A4 double transgenic mice. Additional cell lines expressing both Neu and S100A4 have also been derived by transfection of rat S100A4 cDNA into tumour cell lines cloned from neu single transgenic mice. Using these cells in transfilter migration assays, it has been shown that increases in either motility or invasive properties correlate with each other and with the level of S100A4 protein. Injection of three of the cell lines separately into the mammary fat pads of nude mice showed that elevated levels of S100A4 correlated with the degree of metastasis to the lungs. In contrast, changes in cell proliferation and cell-substrate adhesion did not correlate with S100A4 levels. Neither motility nor invasiveness correlated with proteolytic degradation of gelatin as measured by zymography. Thus, the results suggest that the main effect of increases in S100A4 levels in metastasis is to generate increased cell motility and invasion and that this latter change is not dependent upon an increased ability to degrade the intercellular matrix.
钙结合蛋白S100A4水平升高与乳腺癌患者的不良生存相关，并在啮齿动物模型中诱导转移。为了研究S100A4对转移过程中不同组分的影响，已从neu转基因小鼠的非恶性肿瘤以及neu/S100A4双转基因小鼠的恶性肿瘤中分离出上皮细胞系。通过将大鼠S1O0A4 cDNA转染到从neu单转基因小鼠克隆的肿瘤细胞系中，也获得了另外表达Neu和S100A4的细胞系。在跨滤迁移试验中使用这些细胞，结果表明，运动性或侵袭性的增加彼此相关，并且与S100A4蛋白水平相关。将三个细胞系分别注射到裸鼠的乳腺脂肪垫中，结果显示S100A4水平升高与肺转移程度相关。相反，细胞增殖和细胞与底物黏附的变化与S100A4水平无关。通过酶谱法测定，运动性和侵袭性均与明胶的蛋白水解降解无关。因此，结果表明，转移过程中S100A4水平升高的主要作用是使细胞运动性和侵袭性增加，并且后一种变化不依赖于降解细胞间基质能力的增加。
