Studies on the mechanisms of invasion in cancer. IV. A factor associated with release of neutral protease of tumor cell

A substance capable of releasing a certain neutral protease from rat ascites hepatoma cells was extracted from tumor tissues and partially purified. The substance, which was assumed to be a thermostable peptide, was characterized by prompt action and noncytotoxicity. Intradermal injection of the released neutral protease induced extravascular migration of circulating tumor cells and formation of metastases. No protease could be released from normal hepatic cells. These observations suggested that the released neutral protease might be involved in malignant invasion through production of postulated cancer‐cell‐chemotactic factor. Such a substance was, however, difficult to demonstrate in normal skin. Different factors associated with the release of another neutral protease and an alkaline protease were also found. However, these proteases did not provoke invasion of tumor cells after intradermal injection.