Role of matrix metalloproteinase-9 in in vitro invasion of esophageal carcinoma cells.

Abstract

Although some investigators recently suggested that MMP-9 may play a critical role in invasion and metastasis, along with MMP-2, in esophageal carcinoma, there has been no direct evidence that MMPs play a critical role in the actual invasion of esophageal carcinoma cells. Here, we investigated the role of MMPs in the in vitro invasion of esophageal carcinoma cell lines (TE-series). Our methods included in vitro invasion assay, gelatin zymography, and enzyme-linked immunosorbent assay (ELISA). Four cell lines (but not TE-5) secreted MMP-2 and MMP-9 in the culture medium. Using a quantitative in vitro invasion assay, we found a significant (P = 0.002) correlation between the extent of in vitro invasion and the amount of MMP-9, but not of MMP-2, secreted into the conditioned medium in the four cell lines. In these cell lines, R-94138, a specific MMP-9 inhibitor, inhibited in vitro invasion in a dose-dependent manner. Although TE-5 did not secrete MMP-2 or MMP-9, the cells showed a strong in vitro invasion. Our data suggest that most of the esophageal carcinoma cell lines use MMP-9 for in vitro invasion, but others may use proteinase(s) other than MMP-9.