Enzyme histochemical studies on tumor blood vessels

The oxygenation, the growth rate and the metastatic potential of a solid tumor depend on its vascularization and, in particular, on angiogenesis; a therapeutic approach affecting angiogenesis has been suggested as an alternative to conventional ones. Especially the study of the metabolism in the cells of the vessel wall should be a useful prerequisite for this approach. In this connection, an enzyme histochemical study was performed to characterize the blood vessels in a solid tumor (Ehrlich carcinoma). The following enzymes were considered: (a) alkaline phosphatase, involved in the transcellular phosphate transport and in the response to inflammatory and growth promoting factors; (b) dihydrofolate reductase, involved in the metabolism of tetrahydrofolate (for the synthesis of nucleic acids and the metabolism of serine and glycine); (c) purine nucleoside phosphorylase, involved in the degradation of purines and, in particular, of extracellular ATP and ADP; (d) xanthine oxidoreductase, engaged in the same degradation path and leading to the formation of urate, a strong antioxidant. Various patterns of enzyme activities were observed in the vessel wall. In particular, thin linear capillaries (presumed to be host capillaries penetrating the tumor) were identified for the intense positivity of alkaline phosphatase, dihydrofolate reductase and purine nucleoside phosphorilase; tortuous capillaries with variable diameters (presumed to be induced by angiogenesis from the host vessels) were negative for the alkaline phosphatase and expressed an heterogeneous pattern for the dihydrofolate reductase. All the data suggest a different vessel behaviour concerning the response to cytokines and to inflammatory stimuli.