SUPPRESSION OF GELATINASE PRODUCTION WITH DECREASED INVASIVENESS OF CHORIOCARCINOMA CELLS BY HUMAN RECOMBINANT INTERFERON-BETA

OBJECTIVE: Choriocarcinoma is a highly invasive gynecologic tumor, and hematogenous metastases frequently develop. To establish a molecular basis for antiinvasion therapy of choriocarcinoma, we examined the eff ects of human recombinant interferons an gelatinase production and inv asion by choriocarcinoma cells. STUDY DESIGN: Using five choriocarcino ma cell lines, we measured gelatinase activity by gelatin zymography. The effects of recombinant interferons (rlFN-alpha, rlFN-beta, and rlF N-gamma) were then analyzed by Western blot analysis and chemoinvasion assay. RESULTS: High levels of 72 kd gelatinase activity were detecte d in the highly invasive choriocarcinoma cell lines, two of which also contained an active form of 72 kd gelatinase with an apparent molecul ar mass of 68 kd. Gelatinase production was decreased by incubation wi th rIFN-beta. In the chemoinvasion assay, only rlFN-beta had an inhibi tory effect on the invasiveness of tumor cells without a cytotoxic eff ect. CONCLUSION: Choriocarcinoma cells showed high 72 kd gelatinase ac tivity, which suggested a role for the enzyme in vascular metastasis. Studies on the use of rlFN-beta to inhibit metastasis of choriocarcino ma via suppression of gelatinase production are warranted.