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Characterization of the Mouse IFN-lambda Ligand-Receptor System: IFN-lambdas Exhibit Antitumor Activity Against B16 Melanoma

Characterization of the Mouse IFN-lambda Ligand-Receptor System: IFN-lambdas Exhibit Antitumor Activity Against B16 Melanoma

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

Cancer Res. 2006 Apr 15;66(8):4468-77.

PMID: 16618774

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413322	IFN-lambda 2 from mouse			Price

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