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Platelet-derived endothelial cell growth factor was previously identified as the sole angiogenic activity present in platelets; it is now known to be thymidine phosphorylase (TP). The effect of TP on [methyl-3H]thymidine uptake does not arise from de novo DNA synthesis and the molecule is not a growth factor. Despite this, TP is strongly angiogenic in a rat sponge and freeze-injured skin graft model. Neutralizing antibodies and site-directed mutagenesis confirmed that the enzyme activity 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 breast tissue (P < 0.001). Overexpression of TP in MCF-7 breast carcinoma cells had no effect on growth in vitro but markedly enhanced tumor growth in vivo. These data and the correlation of expression in tumors with malignancy identify TP as a target for antitumor strategies.

Original publication

DOI

10.1073/pnas.92.4.998

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

14/02/1995

Volume

92

Pages

998 - 1002

Keywords

Animals, Breast Neoplasms, Cattle, Cell Division, Cells, Cultured, Chemotaxis, Endothelium, Vascular, Female, Humans, Male, Mice, Mice, Inbred BALB C, Mutation, Neovascularization, Pathologic, Rats, Rats, Wistar, Substrate Specificity, Thymidine Phosphorylase