Induction of matrix metalloproteinase 9 expression in breast carcinoma cells by a soluble factor from fibroblasts.
Tumor-stromal interactions appear to play an important role in the induction of metalloproteinase expression in malignant tumors. We describe a tissue culture system in which expression of MMP-9 (gelatinase B or the 92 kDa type IV collagenase/gelatinase) was induced by co-cultivation of fibroblasts with breast cancer cell lines. While neither the breast cancer cells nor the normal rat embryo fibroblasts made MMP-9 alone in culture, human MMP-9 was made in the co-cultures. The MMP-9 was secreted in a latent form. The induction occurred at least in part through increases in the MMP-9 mRNA levels in the breast cancer cells. These increases did not appear to require protein synthesis. Conditioned medium from the fibroblasts could duplicate the induction of MMP-9 in the breast cancer cell lines. The active factor in the medium was inactivated by heat or by trypsin suggesting that it was a protein. This protein was in the size range of 30-100 kDa. Thus, fibroblasts could secrete a factor which was able to regulate the expression of MMP-9 in breast cancer cells.
Himelstein
B P
BP
Division of Oncology, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, USA.
Muschel
R J
RJ
D000818:Animals; D000911:Antibodies, Monoclonal; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000201:enzymology* / Q000276:immunology; D002277:Carcinoma / Q000378:metabolism*; D002450:Cell Communication; D018920:Coculture Techniques; D017364:Collagenases / Q000096:biosynthesis* / Q000187:drug effects / Q000276:immunology; D016895:Culture Media, Serum-Free; D046508:Culture Techniques / Q000379:methods; D004790:Enzyme Induction; D005260:Female; D005347:Fibroblasts / Q000737:chemistry*; D006801:Humans; D020780:Matrix Metalloproteinase 9; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D014357:Trypsin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D016895:Culture Media, Serum-Free; D012333:RNA, Messenger; D014357:Trypsin; D017364:Collagenases; D020780:Matrix Metalloproteinase 9