IL-27 directly restrains lung tumorigenicity by suppressing cyclooxygenase-2-mediated activities.
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.
Ho
Ming-Yi
MY
Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Department of Education and Research, Taipei City Hospital, Taipei, Taiwan, Republic of China.
Leu
Shr-Jeng Jim
SJ
Sun
Guang-Huan
GH
Tao
Mi-Hua
MH
Tang
Shye-Jye
SJ
Sun
Kuang-Hui
KH
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D014746:Vimentin / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism
C486767:Il27 protein, mouse; D007378:Interleukins; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; D014746:Vimentin; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D051546:Cyclooxygenase 2; D015232:Dinoprostone