Abstract:
: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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Pan Q,Kleer CG,van Golen KL,Irani J,Bottema KM,Bias C,De Carvalho M,Mesri EA,Robins DM,Dick RD,Brewer GJ,Merajver SDsubject
Has Abstractpub_date
2002-09-01 00:00:00pages
4854-9issue
17eissn
0008-5472issn
1538-7445journal_volume
62pub_type
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