Usefulness of expression of protease as biologic marker in 5-FU resistant human colon cancer cell line HT29 / 대한내과학회지

ABSTRACT

There have been many reports that colon cancer responds poorly to chemotherapy. Several classes of matrix metalloproteinases(MMPs) have been implicated in the process of invasion of epithelial and endothelial basement membranes in several steps of tumor invasion and metastasis. This study was performed to determine the biologic behavior and the histopathological characteristics of a 5-FU resistant colon cancer cell line. METHODS: We performed several biologic assays including liver colonization assay, cell adhesion assay, invasion assay and zymogram for protease activity using parental HT29 cell and 5-FU resistant HT29 cell (HT29-FU cell). RESULTS: In liver colonization assay, HT29-FU cell revealed a 2.5-fold increase in the liver weight and tumor burden compared with HT29 cell. HT29-FU cell showed moderate increase in adhesion and invasion assays in comparison to HT29 cell. HT29-FU cell revealed increased activity of MMPs and serine protease. Xenograft tumors of HT29-FU cell formed moderately differentiated adenocarcinoma with more glandular formations of mucin. CONCLUSION: The increased expression of MMPs in 5-FU resistant colon cancer cell can explain poor prognosis. These are potentially poor prognostic indicators in 5-FU resistant colon cancer. Consequently, it can be suggested that modulation of MMPs is needed to prevent invasion and metastasis in colon cancer by using inhibitors of these enzymes.