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Thymidine phosphorylase (TP) (E.C. 2.4.2.4), also known as platelet-derived endothelial cell growth factor, is a potent angiogenic factor. The expression of TP correlates with poor prognosis in a range of tumor types. 2-Deoxy-D-ribose-1-phosphate, a product of thymidine catabolism by TP, is a strongly reducing sugar that generates oxygen radical species during the early stages of protein glycation. We show that thymidine induces oxidative stress in TP-overexpressing carcinoma cells, promoting secretion of the stress-induced angiogenic factors vascular endothelial growth factor and interleukin-8, and inducing matrix metalloproteinase-1. Our findings outline a putative mechanism for TP-induced angiogenesis and identify novel targets for intervention.

Type

Journal article

Journal

Cancer res

Publication Date

15/11/2000

Volume

60

Pages

6298 - 6302

Keywords

Carcinoma, Endothelial Growth Factors, Enzyme-Linked Immunosorbent Assay, Humans, Interleukin-8, Lymphokines, Matrix Metalloproteinase 1, Neovascularization, Pathologic, Oxidative Stress, Thymidine, Thymidine Phosphorylase, Transfection, Tumor Cells, Cultured, Urinary Bladder Neoplasms, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors