INHIBITION OF LYMPHOCYTE-INDUCED ANGIOGENESIS BY FREE-RADICAL SCAVENGERS

Solid tumors induce an angiogenic response by the host blood vessels t o form a new vascular network for the supply of fresh nutrients and ox ygen responsible for tumor growth. Furthermore, tumor growth and metas tatic spread is abrogated or markedly reduced in the absence of neovas cularization. Spleen T lymphocytes from tumor-bearing mice elicit a st rong neovascular response. It is well known that certain T cell respon ses require the presence of active oxygen radicals. Because these meta bolites are produced during tumor growth, we studied whether oxygen fr ee radicals play a role in the angiogenesis induction by lymphocytes. In this study, we demonstrated that the administration of a free radic al scavenger (EGb-761) to tumor-bearing mice, blocked the angiogenic r esponse and decreased the lung metastatic incidence. On the other hand , when normal lymphocytes were incubated with the xanthine-xanthine ox idase system (X-XO), a known superoxide anion generator, this elicited a dose-response positive angiogenic reaction in normal recipient mice . No angiogenic response was observed in the absence of X-XO, or when EGb-761 or superoxide dismutase (SOD) plus catalase (CAT) were added t o the incubation medium. These results suggest that free radicals are involved in some step of the angiogenic process, and that the EGb-761 treatments block this response due to the free radical scavenging acti vity of this compound.