Abstract |
Recently discovered type III IFNs ( IFN-lambda) exert their antiviral and immunomodulatory activities through a unique receptor complex composed of IFN-lambdaR1 and interleukin-10 receptor 2. To further study type III IFNs, we cloned and characterized mouse IFN-lambda ligand-receptor system. We showed that, similar to their human orthologues, mIFN-lambda2 and mIFN-lambda3 signal through the IFN-lambda receptor complex, activate IFN stimulated gene factor 3, and are capable of inducing antiviral protection and MHC class I antigen expression in several cell types including B16 melanoma cells. We then used the murine B16 melanoma model to investigate the potential antitumor activities of IFN-lambdas. We developed B16 cells constitutively expressing murine IFN-lambda2 (B16.IFN-lambda2 cells) and evaluated their tumorigenicity in syngeneic C57BL/6 mice. Although constitutive expression of mIFN-lambda2 in melanoma cells did not affect their proliferation in vitro, the growth of B16.IFN-lambda2 cells, when injected s.c. into mice, was either retarded or completely prevented. We found that rejection of the modified tumor cells correlated with their level of IFN-lambda2 expression. We then developed IFN-lambda-resistant B16.IFN-lambda2 cells (B16.IFN-lambda2Res cells) and showed that their tumorigenicity was also highly impaired or completely abolished similar to B16.IFN-lambda2 cells, suggesting that IFN-lambdas engage host mechanisms to inhibit melanoma growth. These in vivo experiments show the antitumor activities of IFN-lambdas and suggest their strong therapeutic potential.
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Authors | Ahmed Lasfar, Anita Lewis-Antes, Sergey V Smirnov, Shubha Anantha, Walid Abushahba, Bin Tian, Kenneth Reuhl, Harold Dickensheets, Faruk Sheikh, Raymond P Donnelly, Elizabeth Raveche, Sergei V Kotenko |
Journal | Cancer research
(Cancer Res)
Vol. 66
Issue 8
Pg. 4468-77
(Apr 15 2006)
ISSN: 0008-5472 [Print] United States |
PMID | 16618774
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Ligands
- Receptors, Interferon
- Interferons
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Topics |
- Amino Acid Sequence
- Animals
- COS Cells
- Chlorocebus aethiops
- Cloning, Molecular
- Cricetinae
- Female
- Humans
- Interferons
(genetics, immunology)
- Ligands
- Melanoma, Experimental
(genetics, immunology, therapy)
- Mice
- Mice, Inbred C57BL
- Molecular Sequence Data
- Receptors, Interferon
(genetics, immunology)
- Signal Transduction
- Transfection
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