A RIBONUCLEASE INHIBITOR EXPRESSES ANTI-ANGIOGENIC PROPERTIES AND LEADS TO REDUCED TUMOR-GROWTH IN MICE

Our experiments were designed to determine whether recombinant ribonuc lease inhibitor (RNasin) could inhibit angiogenesis and reduce tumor g rowth in adult mice. We used the Fajardo disc angiogenesis assay as th e primary means of measuring new blood vessel growth. This assay measu res the penetration of cells into a polyvinyl alcohol sponge with a ce ntral core of ELVAX-coated sponge containing test substances. Cell pen etration was reduced to 29.3% of control (phosphate-buffered saline; b eat-inactivated RNasin) values. Endothelial cell influx was measured b y lectin staining and confirmed by culturing cells isolated from spong es by collagenase treatment. RNasin also reduced the augmented reactio n evoked by either basic fibroblast growth factor (bFGF) or sodium ort hovanadate. To confirm the anti-angiogenic activity of RNasin. Hydron- coated polyvinyl sponges containing bFGF or bFGF plus RNasin were impl anted into adult mouse corneas. bFGF induced a strong angiogenic respo nse that was almost completely inhibited by RNasin. RNasin-containing ELVAX-coated sponges implanted subcutaneously underneath an intraderma l inoculum of C755 mammary tumor cells caused significant reduction in tumor growth (P < 0.005). The antitumor effect of RNasin correlated w ith its effect on tumor-induced neovascularization, suggesting that th e ability of RNasin to affect tumor growth was due to tis ability to i nhibit angiogenesis.