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IL-27 directly restrains lung tumorigenicity by suppressing cyclooxygenase-2-mediated activities
Ming-Yi Ho1, Shr-Jeng Jim Leu, Guang-Huan Sun
1Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Department of Education and Research, Taipei City Hospital, Taipei, Taiwan, Republic of China.
Abstract:
Gene transfer of IL-27 to tumor cells has been proven to inhibit tumor growth in vivo by antiproliferation, antiangiogenesis, and stimulation of immunoprotection. To investigate the nonimmune mechanism of IL-27 that suppresses lung cancer growth, we have established a single-chain IL-27-transduced murine Lewis lung carcinoma (LLC-1) cell line (LLC-1/scIL-27) to evaluate its tumorigenic potential in vivo. Mice inoculated with LLC/scIL-27 displayed retardation of tumor growth. Production of IL-12, IFN-gamma, and cytotoxic T cell activity against LLC-1 was manifest in LLC/scIL-27-injected mice. Of note, LLC-1/scIL-27 exhibited decreased expression of cyclooxygenase-2 (COX-2) and PGE(2). On the cellular level, the LLC/scIL-27 transfectants had reduced malignancy, including down-regulation of vimentin expression and reduction of cellular migration and invasion. The suppression of tumorigenesis by IL-27 on lung cancer cells was further confirmed by the treatment with rIL-27 on the murine LLC-1 and human non-small cell lung carcinoma (NSCLC) cell lines. PGE(2)-induced vimentin expression, movement, and invasiveness were also suppressed by the treatment with rIL-27. Our data show that IL-27 not only suppresses expression of COX-2 and PGE(2) but also decreases the levels of vimentin and the abilities of cellular migration and invasion. Furthermore, inoculation of LLC/scIL-27 into immunodeficient NOD/SCID mice also exhibited reduced tumor growth. Our data indicate that IL-27-induced nonimmune responses can contribute to significant antitumor effects. Taken together, the results suggest that IL-27 may serve as an effective agent for lung cancer therapy in the future.
Insights
Interleukin-27 (IL-27) gene transfer inhibits lung cancer growth by reducing tumor cell malignancy and invasion. This non-immune mechanism offers potential for novel lung cancer therapies.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Interleukin-27 (IL-27) demonstrates anti-tumorigenic properties through antiproliferation, antiangiogenesis, and immune stimulation.
- The non-immune mechanisms underlying IL-27's suppression of lung cancer growth require further investigation.
Purpose of the Study:
- To investigate the non-immune mechanisms by which IL-27 suppresses lung cancer growth.
- To evaluate the therapeutic potential of IL-27 in lung cancer treatment.
Main Methods:
- Established a single-chain IL-27-transduced murine Lewis lung carcinoma (LLC-1) cell line (LLC-1/scIL-27) for in vivo and in vitro studies.
- Assessed tumor growth, immune responses (IL-12, IFN-gamma, cytotoxic T cell activity), and molecular markers (COX-2, PGE(2), vimentin) in inoculated mice.
- Evaluated the effects of recombinant IL-27 (rIL-27) on LLC-1 and human non-small cell lung carcinoma (NSCLC) cell lines, including their migratory and invasive capabilities.
Main Results:
- LLC-1/scIL-27 inoculation significantly retarded tumor growth in mice.
- IL-27 suppressed cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE(2)) expression, reduced vimentin levels, and decreased cellular migration and invasion.
- IL-27 treatment also suppressed PGE(2)-induced vimentin expression and invasiveness in lung cancer cells, with reduced tumor growth observed even in immunodeficient mice.
Conclusions:
- IL-27 exerts significant anti-tumor effects in lung cancer through non-immune mechanisms, including suppression of COX-2/PGE(2) pathways and reduction of cellular malignancy.
- These findings highlight IL-27's potential as an effective therapeutic agent for lung cancer.
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