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 effects of human recombinant interferons on gelatinase production and invasion by choriocarcinoma cells.


METHODS
Using five choriocarcinoma cell lines, we measured gelatinase activity by gelatin zymography. The effects of recombinant interferons (rIFN-alpha, rIFN-beta, and rIFN-gamma) were then analyzed by Western blot analysis and chemoinvasion assay.


RESULTS
High levels of 72 kd gelatinase activity were detected in the highly invasive choriocarcinoma cell lines, two of which also contained an active form of 72 kd gelatinase with an apparent molecular mass of 68 kd. Gelatinase production was decreased by incubation with rIFN-beta. In the chemoinvasion assay, only rIFN-beta had an inhibitory effect on the invasiveness of tumor cells without a cytotoxic effect.


CONCLUSIONS
Choriocarcinoma cells showed high 72 kd gelatinase activity, which suggested a role for the enzyme in vascular metastasis. Studies on the use of rIFN-beta to inhibit metastasis of choriocarcinoma via suppression of gelatinase production are warranted.
Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Japan.
N
N
Kato
A
A
Nawa
K
K
Tamakoshi
F
F
Kikkawa
N
N
Suganuma
T
T
Okamoto
S
S
Goto
Y
Y
Tomoda
M
M
Hamaguchi
M
M
Nakajima
D002822:Choriocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D005260:Female; D018093:Gelatinases / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology* / Q000627:therapeutic use; D007371:Interferon-gamma / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D011247:Pregnancy; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology
D007370:Interferon Type I; D011994:Recombinant Proteins; D016899:Interferon-beta; D007371:Interferon-gamma; D018093:Gelatinases