Induction of matrix metalloproteinase 9 expression in breast carcinoma cells by a soluble factor from fibroblasts |
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Authors: | Bruce P Himelstein Ruth J Muschel |
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Institution: | (1) Division of Oncology, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA;(2) Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA;(3) Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Room 269, John Morgan Building, 19104 Philadelphia, PA, USA |
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Abstract: | 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. |
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Keywords: | breast carcinoma MMP-9 tumor-host interactions |
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