Differences in the repertoires of basement membrane degrading enzymes in two carcinoma sublines with distinct patterns of site-selective metastasis.

Basement membrane-degrading enzymes of two clonal sublines of the murine Lewis lung carcinoma with distinct patterns of organ-selective metastasis were analyzed. Subline M-27 is highly metastatic to the lung and does not form liver metastases, while subline H-59 is highly metastatic to lymph nodes and liver, but not to lung. Qualitative and quantitative differences in the enzymatic profiles were found. H-59 cells which were significantly more invasive in vitro in the Matrigel invasion assay were found by zymogram analysis to secrete high levels of a 72 kDa gelatinase, while M-27 cells produced low levels of this gelatinase and of a higher molecular weight species which migrated in the 107 kDa region. On the other hand, M-27 cells produced significantly higher levels of urokinase type plasminogen activator (uPA) as indicated by a fibrinolysis assay and by Western blot analysis. Northern blot assays revealed an increase of approx. 3-fold in mRNA for cathepsin B in tumor M-27 which was reflected in a quantitative difference in plasma membrane cathepsin B levels as detected by Western blot analysis. H-59 cells on the other hand expressed approx. 8.5-fold more mRNA for cathepsin L. The quantitative differences in the levels of basement membrane degrading proteinases released by these tumor cells suggest that invasion by these cells is differentially regulated--a possible factor in their distinct patterns of dissemination.