Matrix metalloproteinase-7 expression in colorectal cancer liver metastases: Evidence for involvement of MMP-7 activation in human cancer metastases

Purpose: Matrix metalloproteinase-7 (MMP-7) is a member of the MMP family, which is overexpressed by some tumor cells and is thought to enhance the tumor metastatic potential. The aim of this study is to examine the MMP-7 expression in the human colorectal cancer (CRC) liver metastases and normal liver tissue using multiple techniques and to determine its association with liver metastases formation. Experimental Design: MMP-7 mRNA, protein, and enzymatic levels were determined by reverse transcription-PCR, Western blot analysis, and casein zymography in the specimens of human CRC liver metastases and paired normal liver tissue from 44 patients. The cellular localization of MMP-7 was analyzed by immunohistochemistry. Results: Our data reveal that all of the investigated liver metastases samples overexpressed MMP-7 mRNA and protein compared with the normal liver tissue. By zymogram, higher levels of the latent form of MMP-7 were found in 88.6% (39 of 44) liver metastases samples, whereas normal liver tissue exhibited only trace amounts. The activated form of MMP-7 was only found in those in which the pro-MMP-7 was present (n = 39); in contrast, it was not detected in the normal liver tissues. Immunohistochemically, MMP-7 is localized to the cytoplasm of tumor cells, and the strong signal is concentrated in the tumor front areas. Conclusions: Our observations emphasize the important role of MMP-7 production and activation in human CRC liver metastases formation.