THYMIDINE PHOSPHORYLASE IS ANGIOGENIC AND PROMOTES TUMOR-GROWTH

Platelet-derived endothelial cell growth factor was previously identif ied as the sole angiogenic activity present in platelets; it is now kn own to be thymidine phosphorylase (TP). The effect of TP on [methyl-H- 3]thymidine uptake does not arise from de novo DNA synthesis and the m olecule is not a growth factor. Despite this, TP is strongly angiogeni c in a rat sponge and freeze-injured skin graft model. Neutralizing an tibodies and site-directed mutagenesis confirmed that the enzyme activ ity of TP is a condition for its angiogenic activity. The level of TP was found to be elevated in human breast tumors compared to normal bre ast tissue (P < 0.001). Overexpression of TP in MCF-7 breast carcinoma cells had no effect on growth in vitro but markedly enhanced tumor gr owth in vivo. These data and the correlation of expression in tumors w ith malignancy identify TP as a target for antitumor strategies.