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IL-6 antisense-mediated growth inhibition of a choriocarcinoma cell line: an intracellular autocrine growth mechanism.
- 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.
- Subjects :
- Antibodies, Monoclonal
Antigens, CD genetics
Antigens, CD immunology
Cell Division drug effects
Choriocarcinoma metabolism
Cytokine Receptor gp130
Gene Expression
Humans
Interleukin-6 biosynthesis
Interleukin-6 pharmacology
Membrane Glycoproteins genetics
Membrane Glycoproteins immunology
Receptors, Interleukin genetics
Receptors, Interleukin immunology
Receptors, Interleukin-6
Recombinant Proteins
Tumor Cells, Cultured
Choriocarcinoma pathology
Interleukin-6 genetics
Oligonucleotides, Antisense pharmacology
Subjects
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