Antitumor effect of B16 melanoma cells genetically modified with the angiogenesis inhibitor RNasin

The growth of new blood vessels is an essential condition for the developme nt of tumors with a diameter greater than 1-2 mm and also for their metasta tic dissemination. RNasin, the placental ribonuclease inhibitor, is known t o have antiangiogenic activity through the inhibition of angiogenin and bas ic fibroblast growth factor. Nevertheless, the administration of the recomb inant form of a protein poses several limitations; as a result, we have stu died the antitumor effect of RNasin in a murine gene therapy model. RNasin cDNA was subcloned into the pcDNA3 expression vector, and the resulting rec ombinant plasmid was used to transfect the B16 murine melanoma cell line. A n RNasin inverted construction was used as control. Mice intravenously inje cted with clones expressing RNasin showed a significant inhibition of tumor metastatic progression with respect to control groups ( P < .001) and surv ived longer (P < .001). Tissue sections from RNasin-expressing cell tumors showed a lower number of blood vessels when compared to tissue sections fro m mice lungs that had been inoculated with control cell lines. The results of these experiments show that the genetic modification of tumor cells with RNasin cDNA yields a significant antitumor effect, and suggest that this e ffect is at least partially the result of angiogenesis inhibition.