Journal of Mammary Gland Biology and Neoplasia

, Volume 10, Issue 4, pp 299–310 | Cite as

The Role of Copper in Tumour Angiogenesis

Article

Abstract

Copper stimulates the proliferation and migration of endothelial cells and is required for the secretion of several angiogenic factors by tumour cells. Copper chelation decreases the secretion of many of these factors. Serum copper levels are upregulated in many human tumours and correlate with tumour burden and prognosis. Copper chelators reduce tumour growth and microvascular density in animal models. New orally active copper chelators have enabled clinical trials to be undertaken, and there are several studies ongoing. A unifying mechanism of action by which copper chelation inhibits endothelial cell proliferation and tumour secretion of angiogenic factors remains to be elucidated, but possible targets include copper-dependent enzymes, chaperones, and transporters.

Keywords

Copper chelation Angiogenesis Tetrathiomolybdate Copper-dependent enzymes 

Abbreviations

CCO

cytochrome c oxidase

FGF

fibroblast growth factor

HIF-1

hypoxia inducible factor 1

HUVEC

human umbilical vein endothelial cell

IL-1

interleukin 1

IL-6

interleukin 6

IL-8

interleukin 8

LOX

lysyl oxidase

MTF-1

metal transcription factor 1

NSCLC

non small cell lung cancer

PHD

prolyl hydroxylase domains

SOD-1

superoxide dismutase 1

SOD-2

superoxide dismutase 2

SSAO

semicarbazide-sensitive amine oxidase

TGF

transforming growth factor

TM

tetrathiomolybdate

VAP-1

vascular adhesion protein 1

VEGF

vascular endothelial growth factor

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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  1. 1.Cancer Research UK Medical Oncology UnitThe Churchill HospitalOxfordUK

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