Secretion of proteinases from malignant and nonmalignant human breast tissue.
Both malignant (adenocarcinomas) and nonmalignant (fibroadenomas and normal tissue) human breast tissues were maintained in organ culture for up to 10 days to study the secretion of lysosomal and neutral proteinases. Little difference was observed between the different tissue groups in the release of the lysosomal proteinase cathepsin D into the culture medium. Similar results were obtained when media were tested for plasminogen activator activity. The secretion of collagenolytic activity was investigated with fibroadenoma and adenocarcinoma explants and found to be very low for both tissue groups. The average accumulation of collagenase activity during a 2-day period was 0.002 units/microgram DNA for adenocarcinomas and 0.008 units/microgram DNA for fibroadenomas. The only proteinase that was secreted in substantially higher amounts from explants of malignant tissue was a cathepsin B-like thiol proteinase. Media from adenocarcinoma explants (n = 38) contained on the average 11 times more activity than did media from fibroadenoma (n = 20) and normal tissue explants (n = 8). Metastases of mammary adenocarcinomas (n = 7) secreted the thiol proteinase at about one third of the rate of primary tumors. The secretion of this enzyme is dependent upon protein synthesis as its release was completely inhibited 24 hr after the addition of cycloheximide. In some cases, it was also observed that the presence of sheep serum in the tissue culture medium reduced the accumulation of activity.
D000232:Adenofibroma / Q000201:enzymology*; D001940:Breast / Q000201:enzymology*; D001943:Breast Neoplasms / Q000201:enzymology*; D002277:Carcinoma / Q000201:enzymology*; D002401:Cathepsin B; D002402:Cathepsin D; D002403:Cathepsins / Q000378:metabolism; D005110:Extracellular Space / Q000201:enzymology; D005260:Female; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D003012:Microbial Collagenase / Q000378:metabolism; D009924:Organ Culture Techniques; D010447:Peptide Hydrolases / Q000378:metabolism*; D010960:Plasminogen Activators / Q000378:metabolism
D002403:Cathepsins; D010447:Peptide Hydrolases; D010960:Plasminogen Activators; D002401:Cathepsin B; D002402:Cathepsin D; D003012:Microbial Collagenase