Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Carcinoma / blood supply
-
Carcinoma / enzymology*
-
Carcinoma / metabolism
-
Endothelial Growth Factors / biosynthesis
-
Endothelial Growth Factors / metabolism*
-
Enzyme-Linked Immunosorbent Assay
-
Humans
-
Interleukin-8 / biosynthesis
-
Interleukin-8 / metabolism*
-
Lymphokines / biosynthesis
-
Lymphokines / metabolism*
-
Matrix Metalloproteinase 1 / biosynthesis
-
Matrix Metalloproteinase 1 / metabolism
-
Neovascularization, Pathologic / enzymology
-
Oxidative Stress / drug effects
-
Oxidative Stress / physiology*
-
Thymidine / metabolism
-
Thymidine / pharmacology
-
Thymidine Phosphorylase / biosynthesis
-
Thymidine Phosphorylase / genetics
-
Thymidine Phosphorylase / metabolism*
-
Transfection
-
Tumor Cells, Cultured
-
Urinary Bladder Neoplasms / blood supply
-
Urinary Bladder Neoplasms / enzymology*
-
Urinary Bladder Neoplasms / metabolism
-
Vascular Endothelial Growth Factor A
-
Vascular Endothelial Growth Factors
Substances
-
Endothelial Growth Factors
-
Interleukin-8
-
Lymphokines
-
Vascular Endothelial Growth Factor A
-
Vascular Endothelial Growth Factors
-
Thymidine Phosphorylase
-
Matrix Metalloproteinase 1
-
Thymidine