Contribution of matrilysin (MMP-7) to the metastatic pathway of human colorectal cancers

Background/Aim-Matrilysin is one of the matrix metalloproteinases that has a critical role in tumour invasion, and is often expressed in gastrointesti nal cancers. The aim of this study was to examine the role of matrilysin in metastasis of human colorectal cancers. Patients (Subjects)/Methods-The relation between matrilysin expression and Dukes's type was investigated immunohistochemically in 83 surgically resect ed colorectal cancers, including five with liver metastasis. Moreover, the effects of matrilysin on the in vivo invasive and metastatic potential of c olon cancer cells transfected with matrilysin cDNA were examined after subc utaneous injection into SCID mice. Results-In 46% of primary and all of metastatic liver tumours, over 10% of cancer cells were stained positively for matrilysin. The expression of matr ilysin correlated significantly with the presence of nodal or distant metas tases (p<0.05). In addition, matrilysin transfectants formed invasive tumou rs and multiple liver metastases in SCID mice, without producing any signif icant difference in the subcutaneous tumour growth from mock transfectants. Casein zymography showed that the invading and metastasised tumours showed conspicuous matrilysin activity, which correlated with the number of metas tatic lesions (p<0.001). Conclusions-Matrilysin showed a correlation with metastasis in a cohort of 83 colorectal cancer patients and marked metastatic potentiation in human c olorectal cancer xenografts, indicating that it may play a critical role in the metastatic pathway of colorectal cancers.