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The Role of Copper in Tumour Angiogenesis

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

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.

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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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Lowndes, S.A., Harris, A.L. The Role of Copper in Tumour Angiogenesis. J Mammary Gland Biol Neoplasia 10, 299–310 (2005). https://doi.org/10.1007/s10911-006-9003-7

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