This paper has been peer reviewed.
COPPER AND ANGIOGENESIS: UNRAVELLING A RELATIONSHIP KEY TO CANCER PROGRESSION
Article first published online: 25 MAY 2008
© 2008 UChicago Argonne, LLC, Operator of Argonne National Laboratory. Journal compilation © 2008 Blackwell Publishing Asia Pty Ltd
Clinical and Experimental Pharmacology and Physiology
Volume 36, Issue 1, pages 88–94, January 2009
How to Cite
Finney, L., Vogt, S., Fukai, T. and Glesne, D. (2009), COPPER AND ANGIOGENESIS: UNRAVELLING A RELATIONSHIP KEY TO CANCER PROGRESSION. Clinical and Experimental Pharmacology and Physiology, 36: 88–94. doi: 10.1111/j.1440-1681.2008.04969.x
- Issue published online: 18 JAN 2009
- Article first published online: 25 MAY 2008
- Received 30 October 2007; revision 7 March 2008; accepted 11 March 2008.
- endothelial cells;
- synchrotron radiation;
- X-ray fluorescence;
- X-ray imaging
- 1Angiogenesis, the formation of new capillaries from existing vasculature, is a critical process in normal physiology as well as several physiopathologies. A desire to curb the supportive role angiogenesis plays in the development and metastasis of cancers has driven exploration into anti-angiogenic strategies as cancer therapeutics. Key to this, angiogenesis additionally displays an exquisite sensitivity to bioavailable copper. Depletion of copper has been shown to inhibit angiogenesis in a wide variety of cancer cell and xenograft systems. Several clinical trials using copper chelation as either an adjuvant or primary therapy have been conducted. Yet, the biological basis for the sensitivity of angiogenesis remains unclear. Numerous molecules important to angiogenesis regulation have been shown to be either directly or indirectly influenced by copper, yet a clear probative answer to the connection remains elusive.
- 2Measurements of copper in biological systems have historically relied on techniques that, although demonstrably powerful, provide little or no information as to the spatial distribution of metals in a cellular context. Therefore, several new approaches have been developed to image copper in a biological context. One such approach relies on synchrotron-derived X-rays from third-generation synchrotrons and the technique of high resolution X-ray fluorescence microprobe (XFM) analysis.
- 3Recent applications of XFM approaches to the role of copper in regulating angiogenesis have provided unique insight into the connection between copper and cellular behaviour. Using XFM, copper has been shown to be highly spatially regulated, as it is translocated from perinuclear areas of the cell towards the tips of extending filopodia and across the cell membrane into the extracellular space during angiogenic processes. Such findings may explain the heightened sensitivity of this cellular process to this transition metal and set a new paradigm for the kinds of regulatory roles that the spatial dynamics of cellular transition metals may play.