Angiogenic effect of thymidine phosphorylase on macrophages in glioblastoma multiforme

Object. Thymidine phosphorylase (TP) and vascular endothelial growth factor (VEGF) are known angiogenic factors; however, there are few reports in whi ch the relationship between these two factors is addressed. The authors com pared expression patterns of TP and VEGF and investigated their role in the angiogenesis of glioblastoma multiforme (GBM). Methods. Surgical specimens from 41 cases of GEM were immunohistochemically stained for TP, VEGF, CD68 (a macrophage marker), and CD31 (an endothelial cell marker). Both TP labeling indices and VEGF immunoreactivity displayed significant correlations with vascular density. Although VEGF was diffusel y distributed in the tumor, TP was strongly expressed around blood vessels and in vascular proliferation. Double labeling for TP and CD68 in 10 cases indicated that cells that reacted strongly positive for TP were almost alwa ys macrophages, and only small numbers of CD68-negative cells weakly expres sed TP. The TP messenger (m)RNA expression was investigated using reverse transcrip tion-polymerase chain reaction in six GBMs. All six specimens expressed TP mRNA. In addition, TP mRNA was detected in two of three groups of cultured GEM cells derived from surgical specimens. Macrophages, the production of w hich was induced from two volunteers' peripheral blood monocytes by applyin g macrophage colony-stimulating factor, also expressed TP mRNA. The glioma cell lines U251MG and U87MG, which barely express TP mRNA under normal cond itions, expressed TP mRNA in response to interferon-p stimulation or while in an anoxic condition. Conclusions. Although it is feasible that GEM cells can express TP dependin g on their growing conditions, the majority of TP-expressing cells present in GBMs appear to be infiltrating macrophages. Coexistence of VEGF and TP m ay indicate a synergistic upregulation for angiogenesis because VEGF exerts a chemotactic activity on macrophages that express TP.