PLATELET-DERIVED ENDOTHELIAL-CELL GROWTH-FACTOR THYMIDINE PHOSPHORYLASE EXPRESSION IN NORMAL-TISSUES - AN IMMUNOHISTOCHEMICAL STUDY

Angiogenesis is the formation of new blood vessels from the existing v ascular bed. It is a complex multi-step process controlled by a number of angiogenic factors. One such factor is platelet-derived endothelia l cell growth factor (PD-ECGF), recently shown to be thymidine phospho rylase (TP), which is angiogenic in several in vivo assays and tumour systems. PD-ECGF/TP catalyses the reversible phosphorylation of thymid ine to deoxyribose-1-phosphate and thymine. Since PD-ECGF/TP has an im portant role in cellular metabolism and in angiogenesis and its expres sion has been only partially characterized, we raised a monoclonal ant ibody against recombinant PD-ECGF/TP and used an immunohistochemical a pproach to examine the expression of PD-ECGF/TP in a comprehensive ran ge of normal human tissues. The clone P-GF44.C, which recognizes recom binant PD-ECGF/TP and cell lysates transfected with a plasmid expressi ng PD-ECGF/TP cDNA on Western blotting, was selected for its ability t o stain routinely processed tissue. Staining was observed in both the cytoplasm and/or the nucleus. Immunoreactivity was strongly expressed by macrophages, stromal cells, glial cells, and some epithelia. Gastro intestinal epithelium, smooth muscle, adrenal, lung, and testis were n egative. Although endothelial cell expression was observed, there was no correlation with sites of new vessel growth. This pattern of expres sion suggests tight PD-ECGF/TP regulation and that cellular thymidine pools may serve to control its different functions. Thus, in the nucle us it might modulate the pool for DNA synthesis, whilst in the cytopla sm it could control other effects through different enzyme systems. Th e high expression present in macrophages and skin might be important f or total body thymidine homeostasis.