Effect of phorbol ester and cytokines on matrix metalloproteinase and tissue inhibitor of metalloproteinase expression in tumor and normal cell lines.

The effect of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and the cytokines interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) on matrix metalloproteinases (MMP) and metalloproteinase inhibitors was studied in a variety of human cell lines. Expression of the mammalian collagenase (MMP-1), 72-kD gelatinase/type IV collagenase (MMP-2), stromelysin (MMP-3), 92-kD gelatinase/type IV collagenase (MMP-9), and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) was assessed by zymography and Northern blot analysis. MMP-2 and TIMP-2 activities were refractory to TPA, IL-1 and TNF-alpha treatment in most of the cell lines.

Ras levels and metalloproteinase activity in normal versus neoplastic rat mammary tissues.

We have previously reported that activated ras oncogenes can simultaneously switch on the metastatic phenotype and increased capability to degrade type IV collagen. Here the relationship between c-H-ras, metalloproteinase expression and metastatic behavior was studied in N-nitrosomethylurea (NMU)-induced rat mammary carcinomas, which are known to possess activated c-H-ras. When comparing normal rat breast tissue to mammary carcinomas there was no direct relationship between ras DNA levels and neoplastic changes.

Studies on the ability of 65-kDa and 92-kDa tumor cell gelatinases to degrade type IV collagen.

Two major gelatinolytic metalloproteinases (gelatinases) of 65 kDa and 92 kDa were purified from a tumor cell line. Analysis of collagen degradation showed that native full-length Engelbreth-Holm-Swarm (EHS) type IV collagen was not cleaved by the purified gelatinases under conditions where native pepsin-extracted human placental type IV and V collagen and heat-denatured collagens were markedly degraded. However, EHS type IV collagen degradation was noted at 37 degrees C, i.