Published in Cancer Detection and Prevention 1996; 20(5).
Expression of matrix metalloproteinase, matrilysin in human gastrointestinal cancers1Sapporo Medical University; 2Dept Internal Medicine I, Sapporo Medical University, Sapporo, Japan
AIM: To clarify the relationship between matrilysin expression and cancer cell invasion, and to investigate how to prevent colorectal cancer cell invasion by suppression of matrilysin expression. METHODS: Expression of matrilysin was investigated by Northern blot, immunostaining and casein zymography. Invasive ability was assessed by in vitro system using Matrigel and by transplantation of matrilysin-transfected cells in SCID mice. RESULTS: Most of advanced colon and gastric cancers expressed activated form of matrilysin. Enhanced activation observed in hepatocellular carcinomas was significantly correlated with intrahepatic metastasis or tumor thrombus in the portal vein. In vitro invasiveness of matrilysin-transfected cells was greater than that of non-transfected ones. The mice transplanted matrilysin-expressed cells had liver metastases in proportion to matrilysin secretion levels. Suppression of matrilysin expression by transfer of anti-sense matrilysin cDNA resulted in a decrease of invasive ability. All-trans retinoic acid (ATRA) reduced the expression of matrilysin levels. Oral administration of AFRA decreased invasive ability of transplanted tumors which overexpress matrilysin in SCID mice. CONCLUSIONS: Matrilysin has an important role in the development of various gastrointestinal cancers. ATRA will be of benefit to anti-invasion therapy of gastrointestinal cancers.
Paper presented at the International Symposium on the Impact of Cancer Biotechnology on Diagnostic and Prognostic Indicators; Nice, France; October 26 - 28, 1996; in the section on Metastasis.