血管生成
癌症研究
血管内皮生长因子
碱性成纤维细胞生长因子
成纤维细胞生长因子
新生血管
癌症
转录因子
医学
生物
内科学
内分泌学
生长因子
受体
血管内皮生长因子受体
生物化学
基因
作者
Quintin Pan,Celina G. Kleer,Kenneth L. van Golen,Jennifer Irani,Kristen M. Bottema,Carlos Bias,Magda De Carvalho,Enrique A. Mesri,Diane M. Robins,Robert Dick,George J. Brewer,Sofía D. Merajver
出处
期刊:PubMed
日期:2002-09-01
卷期号:62 (17): 4854-9
被引量:119
摘要
Copper plays an essential role in promoting angiogenesis. Tumors that become angiogenic acquire the ability to enter a phase of rapid growth and exhibit increased metastatic potential, the major cause of morbidity in cancer patients. We report that copper deficiency induced by tetrathiomolybdate (TM) significantly impairs tumor growth and angiogenesis in two animal models of breast cancer: an inflammatory breast cancer xenograft in nude mice and Her2/neu cancer-prone transgenic mice. In vitro, TM decreases the production of five proangiogenic mediators: (a) vascular endothelial growth factor; (b) fibroblast growth factor 2/basic fibroblast growth factor; (c) interleukin (IL)-1alpha; (d) IL-6; and (e) IL-8. In addition, TM inhibits vessel network formation and suppresses nuclear factor (NF)kappaB levels and transcriptional activity. Our study suggests that a major mechanism of the antiangiogenic effect of copper deficiency induced by TM is suppression of NFkappaB, contributing to a global inhibition of NFkappaB-mediated transcription of proangiogenic factors.
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