Rat mammary carcinoma cells secrete active collagenase and activate latent enzyme in the stroma via plasminogen activator

Abstract

A spontaneous mammary adenocarcinoma (AC) from an inbred female rat was investigated with regard to secretion of neutral proteases. Cultures of neoplastic epithelial cells derived from the tumour secreted an enzyme that fulfilled the criteria for a specific collagenase. In contrast to cultures of non‐neoplastic cells, tumour collagenase was present as an active enzyme, since treatment with trypsin or p‐aminophenylmercuric acetate (APMA) did not increase activity. The neoplastic cells were also prolific producers of plasminogen activator (PA). Dexamethasone (Dex) (10⁻⁶M) markedly reduced the levels of both enzymes. Addition of tranexamic acid (TA), an inhibitor of plasmin and of plasminogen activation, did not affect collagenase activity, even at 10⁻¹M TA, nor did latent collagenase accumulate. Latent collagenase was secreted in culture by normal fibroblasts from neonatal rat lungs. This latent enzyme was activated by the addition of tumour cell medium plus plasminogen, but this effect was inhibited by the addition of TA. These results demonstrate that the neoplastic cells themselves secrete collagenase as an active enzyme. PA is also secreted, is not involved with tumour collagenase, but is capable, in the presence of plasminogen, of activating latent collagenase produced by the non‐neoplastic cells within the tumour or in the surrounding tissue. This tumour possesses potent collagenolytic ability in vitro which may be partly responsible for its rapid invasion in vivo.