Overexpression of a set of genes, including WISP-1, common to pulmonary metastases of both mouse D122 Lewis lung carcinoma and B16-F10.9 melanoma cell lines.
Overexpression of a set of genes, including WISP-1, common to pulmonary metastases of both mouse D122 Lewis lung carcinoma and B16-F10.9 melanoma cell lines.
复制标题
一组基因（包括WISP-1）的过表达，这是小鼠D122 Lewis Lung Carcinoma和B16-F10.9黑色素瘤细胞系共有的。
DOI：
10.1038/sj.bjc.6600977
复制
发表时间：
2003-07-21
影响因子：
8.8
通讯作者：
Berger, R
中科院分区：
文献类型：
--
作者：
Margalit, O;Eisenbach, L;Amariglio, N;Kaminski, N;Harmelin, A;Pfeffer, R;Shohat, M;Rechavi, G;Berger, R
尽管实体瘤的治疗取得了进步，但转移的发展仍然是癌症患者最重要的问题和死亡原因。为了确定肺转移的遗传决定因素，我们应用寡核苷酸微阵列建立了高度转移性 D122 Lewis 肺癌和 B16-F10.9 黑色素瘤细胞系的小鼠模型。这些模型的特点是 C57BL/6J 小鼠的原发性皮下生长、微小残留病灶和自发性肺转移的时期。微阵列分析确定了 7 个基因，即精氨酸酶、脑钠尿肽 (BNP)、白介素 1 α (IL-1 α)、纤溶酶原激活剂抑制剂 2 (PAI-2)、表面活性蛋白 C (SP-C)、子宫珠蛋白 (UG) 和 wnt-1 诱导的分泌蛋白 1 (WISP-1)，这些基因在肺组织中持续升高。 D122 和 B16-F10.9 模型的转移灶与原发肿瘤相比。先前的研究表明，这七个基因中的两个，IL-1α和PAI-2，参与了转移过程。微阵列获得的结果通过实时定量 PCR 得到了证实，针对三个选定的基因——PAI-2、WISP-1 和 UG。我们的方法旨在识别一般转移过程和具体肺转移所必需的基因。进一步的研究应该解决这些基因在肺部转移过程中的确切作用，并测试它们是否可以用作未来治疗的靶标。
Despite advances in the management of solid tumours, the development of metastases continues to be the most significant problem and cause of death for cancer patients. To define genetic determinants of pulmonary metastases, we have applied oligonucleotide microarrays to established murine models of highly metastatic D122 Lewis lung carcinoma and B16-F10.9 melanoma cell lines. These models are characterised by primary subcutaneous growth in C57BL/6J mice, a period of minimal residual disease and spontaneous pulmonary metastases. Microarray analysis defined seven genes, namely – arginase, brain natriuretic peptide (BNP), interleukin-1 alpha (IL-1 alpha), plasminogen activator inhibitor-2 (PAI-2), surfactant protein C (SP-C), uteroglobin (UG) and wnt-1-induced secreted protein-1 (WISP-1), which were consistently elevated in pulmonary metastases compared to the primary tumour of both D122 and B16-F10.9 models. Previous studies demonstrated that two of these seven genes, IL-1 alpha and PAI-2, are involved in the metastatic process. The results obtained by the microarrays were confirmed by real-time quantitative PCR, for three chosen genes – PAI-2, WISP-1 and UG. Our approach aimed to identify genes essential for the metastatic process in general and for pulmonary metastases specifically. Further research should address the precise role of these genes in the metastasising process to the lungs and test if they could be used as targets for future therapies.