A variable neovascularization threshold in tumor-bearing mice

The development of solid tumors is dependent on angiogenesis in such a way that a restriction in neovascularization would cause secondary tumor implants to remain in dormant state, establishing an apparent paradox. In this study an attempt has been made to demonstrate that in the tumor-host relationship a variable threshold of angiogenic response is generated which can be normal, enhanced or diminished depending on the intensity of the stimulus. The latter was determined by the number of PEM, semiallogeneic lynphocytes or irradiated tumor cells which were intradermally injected to induce the host angiogenic response. As compared to the normal controls, in tumor-bearing mice, capillary neoformation i) induced by a low angiogenic stimulus was progressively inhibited by tumor growth; ii) when induced by higher stimuli, in 9 day tumor-bearing mice the response was enhanced while in those of 12 days it was normal being completely inhibited in 15 day tumor-bearing mice; iii) when in a specific day of tumor growth (9, 12 or 15) progressively higher angiogenic stimuli were applied, the response was higher in tumor-bearing mice than in the corresponding controls. Similar results were obtained with PEM induced granulomas, suggesting the participation of a phenomenon of counter-inflammation. It can be concluded that there is an angiogenic threshold that increases as a function of tumor growth so that the response will depend on whether the stimulus attains or surpasses the threshold.