Host expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in normal colon tissue affects metastatic potential of colorectal cancer.

Abstract

To clarify the mechanism of cancer cell invasion, we paid close attention to the role of matrix metalloproteinases and tissue inhibitors of metalloproteinases in normal tissue that is located in the same organ as the cancer. Samples were obtained from a tumor lesion and normal tissue in the resected large intestine of 59 patients with colorectal cancer, including 13 cases with liver metastasis (Group A) and 46 cases without liver metastasis (Group B). In each sample the expression of m-RNA for matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 was examined using reverse transcription-coupled polymerase chain reaction and southern hybridization. In normal colon tissue the expression rate of matrix metalloproteinase-2 in Group A (76.9 percent) was significantly higher than that of Group B (15.2 percent; P < 0.0001). Regarding the expression pattern of m-RNA of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in normal colon tissue, Group B included 24 cases with matrix metalloproteinase-2 negative, and tissue inhibitor of metalloproteinase-2 positive (24/46; 52.2 percent). Conversely, Group A had only one case with matrix metalloproteinase-2 negative and tissue inhibitor of metalloproteinase-2 positive (1/13; 7.7 percent; P = 0.0107). In addition, the ratio of cases with matrix metalloproteinase-2 positive and tissue inhibitor of metalloproteinase-2 negative in Group A was 30.8 percent (4/13), which was a significantly higher rate than that in Group B (3/46; 6.5 percent; P = 0.0170). We think that the expression pattern of m-RNA of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in normal colon tissue is closely related to liver metastasis in colon cancer patients.