Characterization of the mouse IFN-lambda ligand-receptor system: IFN-lambdas exhibit antitumor activity against B16 melanoma
| Autor: | Ahmed Lasfar, Walid Abushahba, Bin Tian, Shubha Anantha, Faruk G. Sheikh, Anita Lewis-Antes, Kenneth R. Reuhl, Sergei V. Kotenko, Sergey V. Smirnov, Raymond P. Donnelly, Elizabeth Raveche, Harold L. Dickensheets |
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| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
Cell type Receptor complex medicine.medical_treatment Molecular Sequence Data Melanoma Experimental Biology Ligands Transfection Mice Interferon Cricetinae Chlorocebus aethiops medicine Animals Humans Amino Acid Sequence Cloning Molecular neoplasms Receptors Interferon COS cells In vitro Mice Inbred C57BL Cytokine Oncology Immunology COS Cells Cancer research Female Interferons Signal transduction medicine.drug Signal Transduction |
| Zdroj: | Cancer research. 66(8) |
| ISSN: | 0008-5472 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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