SUPPRESSIVE EFFECTS OF RECOMBINANT HUMAN CU, ZN-SUPEROXIDE DISMUTASE ON LUNG METASTASIS OF MURINE TUMOR-CELLS

The inhibitory effect of recombinant human Cu++Zn++ superoxide dismuta se (rhSOD) on metastasis of tumor cells in the mouse was investigated. In an experimental pulmonary metastasis model employing Meth A cells as inoculum, significant inhibition of metastasis was obtained by intr avenous pre- and post-administration of rhSOD. An inhibitory effect of rhSOD was also observed in a spontaneous pulmonary metastasis model w ith 3LL cells as the inoculum. rhSOD was not observed to have any sign ificant effects on the platelet-aggregating activity of tumor cells, t he adhesiveness of tumor cells to vascular components (endothelial cel ls, laminin and type-IV collagen), or the growth of tumor cells either in vitro or in vivo. However, rhSOD suppressed invasion of Meth A and 3LL cells into Matrigel (an artificially reconstituted basement membr ane of collagen, laminin and heparan sulfate) in the presence of hypox anthine and xanthine oxidase, in vitro producers of superoxide. Thus, the present study shows that rhSOD is able to inhibit both experimenta l and spontaneous pulmonary metastasis, possibly through the suppressi on of tumor cell invasion into the extracellular matrix. (C) 1994 Wile y-Liss, Inc.