A neutral protease was extracted from rat ascites hepatoma cells and effectively purified by fractionation with ammonium sulfate followed by chromatography using TEAE-cellulose and hydroxylapatite in that order. The protease eluted in I20 m M phosphate buffer ( p H 6.8) oil hydroxylapatite, on experimental injection, produced locally a factor chemotactic for cancer cells and induced an extravascular emigration of circulating tumor cells followed by a formation of metastatic secondary tumors. Zt was SH-independent or metal-independent. The separation of the protease from nucleic acid was performed by disc electrophoresis. By contrast, another neutral protease, alkaline protease and acid protease from the same cells were negative in causing an extravascular emigration of circulating tumor cells.As described in previous papers (Hayashi et al., 1970;Yoshida et al., 1970), a substance chemo-
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