The major excreted protein of transformed fibroblasts is an activable acid-protease.

Malignant transformation of mouse cells by a variety of agents or treatment with the tumor promoter 12-O-tetradecanoylphorbol 13-acetate or platelet-derived growth factor results in increased synthesis and secretion of a 39,000-dalton protein termed major excreted protein (MEP). We report here that secreted MEP is an acid-activable protease. The secreted precursor form of the protease is auto-activated at low pH and is able to digest a variety of proteins, including the extracellular matrix proteins fibronectin, collagen, and laminin. MEP protease activity has pH optimum of 3.3-3.6 and is temperature- and concentration-dependent. The activity is inhibited by sulfhydryl protease inhibitors such as leupeptin and iodoacetic acid and not by metallo-, seryl-, or carboxyprotease inhibitors. The MEP-derived protease has characteristics distinct from the cathepsins previously reported and thus may be a new acid-protease of mouse cells.