Copper deficiency induced by tetrathiomolybdate suppresses tumor growth and angiogenesis

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 D. Dick, George J. Brewer, Sofia D. Merajver

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309 Scopus citations

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)-1α; (d) IL-6; and (e) IL-8. In addition, TM inhibits vessel network formation and suppresses nuclear factor (NF)κB levels and transcriptional activity. Our study suggests that a major mechanism of the antiangiogenic effect of copper deficiency induced by TM is suppression of NFκB, contributing to a global inhibition of NFκB-mediated transcription of proangiogenic factors.

Original languageEnglish (US)
Pages (from-to)4854-4859
Number of pages6
JournalCancer Research
Volume62
Issue number17
StatePublished - Sep 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Pan, Q., Kleer, C. G., Van Golen, K. L., Irani, J., Bottema, K. M., Bias, C., De Carvalho, M., Mesri, E. A., Robins, D. M., Dick, R. D., Brewer, G. J., & Merajver, S. D. (2002). Copper deficiency induced by tetrathiomolybdate suppresses tumor growth and angiogenesis. Cancer Research, 62(17), 4854-4859.