Purification and characterization of a novel cytotoxic protein from transformed fibroblasts.

The mechanism by which cancer cells overwhelm normal parenchymal cells during cancer invasion remains obscure. In this article, we describe the purification of a potent cytotoxic protein from plasma membranes of ras oncogene transformed fibroblasts. Tumor cytotoxic protein was purified from detergent extracted tumor membranes by anion exchange and gel filtration chromatography. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate indicated that the hemolytic fractions contained a single protein with an apparent molecular weight of 62,000. A higher concentration of tumor cytotoxic protein was required to lyse fibroblasts as compared to RBC. Based on plasma membrane localization, immunological identity, and biological characteristics, tumor cytotoxic protein is a novel cytolysin which is capable of killing normal cells during cancer invasion.