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Decreased Expression of Tissue Inhibitor of Metalloproteinases in Metastatic Tumor Cells Leading to Increased Levels of Collagenase Activity¹

Institut du Cancer de Montréal, Montréal, Québec, Canada H2L 4M1

We have examined the expression of murine tissue inhibitor of metalloproteinases (TIMP) in nonmetastatic and metastatic cell lines derived from SP1 murine mammary adenocarcinoma cells. We observed decreased levels of TIMP mRNA and activity in metastatic cells as compared to their nonmetastatic equivalents in the absence of fetal bovine serum. Lower levels of TIMP mRNA correlated to decreased levels of transcription of the TIMP gene. Net collagenase activity was higher in metastatic cells, but metastatic and nonmetastatic cells secreted similar levels of total collagenase (mainly type IV). This suggests that decreased TIMP gene expression results in increased net collagenase activity in malignant cells.

¹ This work was supported by the National Cancer Institute of Canada.

² Recipient of a studentship from the Cancer Research Society, Inc.

³ Present address: University of Toronto, Charles H. Best Institute, 112 College Street, Toronto, Ontario, Canada, M5G 1L6.

⁴ To whom requests for reprints should be addressed, at Institut du Cancer de Montréal, 1560 Sherbrooke East, Montréal, Québec, Canada H2L 4M1.

Received 9/ 5/90. Accepted 2/ 6/91.

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