Ns. Brown et al., Thymidine phosphorylase induces carcinoma cell oxidative stress and promotes secretion of angiogenic factors, CANCER RES, 60(22), 2000, pp. 6298-6302
Thymidine phosphorylase (TP) (E,C, 2,4,2,4), also known as platelet-derived
endothelial cell growth factor, is a potent angiogenic factor. The express
ion of TF 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 strong
ly reducing sugar that generates oxygen radical species during the early st
ages of protein glycation, We show that thymidine induces oxidative stress
in TP-overexpressing carcinoma cells, promoting secretion of the stress-ind
uced angiogenic factors vascular endothelial growth factor and interleukin-
8, and inducing matrix metalloproteinase-1, Our endings outline a putative
mechanism for TP-induced angiogenesis and identify novel targets for interv
ention.