Reduction of tumour bed effect after angiogenic stimulation

A new two-tumour system has been developed to examine the effect of an angiogenic stimulus on the tumour bed effect (TBE) in C3H mouse skin treated with 20 Gy X rays. The first tumour was implanted intradermally to stimulate angiogenesis. The Lewis lung carcinoma (3LL) was used for this since it is isogeneic in C57 B1 mice and after initial growth (mean volume 69 mm3), tumours completely regressed within 24 days. The second tumour, the RIF-1 fibrosarcoma (RIF) isogeneic to C3H mice was used to assess stromal function using the TBE assay. After complete regression of the 3LL tumour, RIF cells were implanted into the centre of the stimulated sites and 24 days later the resulting RIF tumours were excised and the TBE measured from the yield of viable RIF cells obtained from each tumour. There was an approximately 10-fold increase in cell yield from tumours implanted into stimulated, pre-irradiated beds compared with those implanted into unstimulated, pre-irradiated beds. This suggests that the angiogenic stimulus provided by the growth of the 3LL tumour led to a substantial restoration of the capacity of the radiation-damaged stroma to support tumour growth. If stromal restoration, as seen during these experiments using artificially induced angiogenesis, was to occur in unstimulated stroma during the normal course of repair and regeneration, this slowly dividing tissue constituent might eventually recover given sufficient time. This raises the possibility that the role of the stroma in late radiation damage might not be as important as was previously thought.