Collagenases in human breast carcinoma cell lines.
The intense stromal response to some human tumors is termed the desmoplastic reaction. It is found with most human breast carcinomas. Dissolution of this response, containing predominantly fibrous proteins such as collagen and elastin, can occur with treatment. We have undertaken a study of the collagenases of the breast tumor desmoplastic reaction using a tissue culture model composed of human breast tumor cell lines and various human fibroblasts. The breast tumor cells had the higher collagenase activity, particularly the ZR75-31A cell line. Activity was 10-fold higher than that of the stromal cells. The enzyme was secreted into the media and required trypsin pretreatment for activity to be manifest. Partial purification was achieved of the major collagenase species. The protein was a metalloprotease and, like other mammalian collagenases, had a relative molecular weight of 60,000. Classical 3/4 and 1/4 cleavage products of the triple helical collagen substrate were demonstrated, typical of most mammalian collagenases. Only types I and III collagens were suitable substrates for this enzyme, with no apparent preference between the two. The breast tumor collagenases were not responsive to hormones; however, stimulation of activity was apparent in the absence of proteolytic pretreatment. This may represent conversion of the procollagenases of the breast tumor cells to the active form by an estrogen-sensitive plasminogen activator secreted by the same tumor cells.
D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002460:Cell Line; D003094:Collagen / Q000378:metabolism*; D004848:Epithelium / Q000201:enzymology; D004958:Estradiol / Q000494:pharmacology; D005109:Extracellular Matrix / Q000502:physiology; D005347:Fibroblasts / Q000201:enzymology; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D003012:Microbial Collagenase / Q000302:isolation & purification / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D013379:Substrate Specificity
D006728:Hormones; D011374:Progesterone; D004958:Estradiol; D003094:Collagen; D003012:Microbial Collagenase