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IL-6 antisense-mediated growth inhibition of a choriocarcinoma cell line: an intracellular autocrine growth mechanism.

Authors :
Kong B
Isozaki T
Sasaki S
Source :
Gynecologic oncology [Gynecol Oncol] 1996 Oct; Vol. 63 (1), pp. 78-84.
Publication Year :
1996

Abstract

The growth of tumor cells can be regulated by a variety of cytokines. To investigate the pathogenesis of choriocarcinoma and explore a new therapeutic approach for the carcinoma, we examined the role of IL-6 in the growth of a human choriocarcinoma cell line (JEG-3). IL-6 was identified in the supernatant of the cell culture medium by enzyme-linked immunosorbent assay, indicating that this cell secreted IL-6. The mRNAs of IL-6, IL-6 receptor and gP130, the IL-6 signal transducer, in this cell were shown to be present by reverse transcriptase polymerase chain reaction assay and confirmed by Southern blot hybridization and direct sequencing. The addition of hrIL-6 to the cell culture failed to stimulate cell growth. Monoclonal antibodies against IL-6, IL-6 receptor, and gP130 were also unable to inhibit the proliferation of this cell line. The antisense oligonucleotides targeting IL-6 mRNA, however, inhibited both cell growth and IL-6 production. Taken together, these findings indicate that endogenous IL-6 plays an important role in the growth of the JEG-3 cell line, and it exerts its action by an intracellular autocrine growth mechanism. The results also suggest that the therapeutic trials with monoclonal antibodies designed to neutralize IL-6 or block its receptor will likely fail, whereas the antisense oligonucleotides targeted to IL-6 mRNA may have some value for the treatment of choriocarcinoma and other cancers with intracellular autocrine growth fashion mediated by IL-6.

Details

Language :
English
ISSN :
0090-8258
Volume :
63
Issue :
1
Database :
MEDLINE
Journal :
Gynecologic oncology
Publication Type :
Academic Journal
Accession number :
8898173
Full Text :
https://doi.org/10.1006/gyno.1996.0282