Role of copper in tumour angiogenesis--clinical implications.
The formation of new blood vessels is the initial step in progressive tumour development and metastasis. The first stage in tumour angiogenesis is the activation of endothelial cells. Copper ions stimulate proliferation and migration of endothelial cells. It has been shown that serum copper concentration increases as the cancer disease progresses and correlates with tumour incidence and burden. Copper ions also activate several proangiogenic factors, e.g., vascular endothelial growth factor, basic fibroblast growth factor, tumour necrosis factor alpha and interleukin 1. This review concerns a brief introduction into the basics of tumour blood vessel development as well as the regulatory mechanisms of this process. The role of copper ions in tumour angiogenesis is discussed. The new antiangiogenic therapies based on a reduction of copper levels in tumour microenvironment are reviewed.
Laboratory of Tumor Immunology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, UI. R Weigla 12, 53-114 Wroclaw, Poland.
Anna
A
Nasulewicz
Andrzej
A
Mazur
Adam
A
Opolski
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D002216:Captopril / Q000627:therapeutic use; D002614:Chelating Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003300:Copper / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D015032:Zinc / Q000627:therapeutic use
D020533:Angiogenesis Inhibitors; D002614:Chelating Agents; D003300:Copper; D002216:Captopril; D015032:Zinc