Abstract
Fas ligand (FasL) is produced by activated T cells and natural killer cells and it induces apoptosis (programmed cell death) in target cells through the death receptor Fas/Apo1/CD95 (ref. 1). One important role of FasL and Fas is to mediate immune-cytotoxic killing of cells that are potentially harmful to the organism, such as virus-infected or tumour cells1. Here we report the discovery of a soluble decoy receptor, termed decoy receptor 3 (DcR3), that binds to FasL and inhibits FasL-induced apoptosis. The DcR3 gene was amplified in about half of 35 primary lung and colon tumours studied, and DcR3 messenger RNA was expressed in malignant tissue. Thus, certain tumours may escape FasL-dependent immune-cytotoxic attack by expressing a decoy receptor that blocks FasL.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Nagata, S. Apoptosis by death factor. Cell 88, 355–365 (1997).
Smith, C. A., Farrah, T. & Goodwin, R. G. The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death. Cell 76, 959–962 (1994).
Simonet, W. S.et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89, 309–319 (1997).
Suda, T., Takahashi, T., Golstein, P. & Nagata, S. Molecular cloning and expression of Fas ligand, a novel member of the TNF family. Cell 75, 1169–1178 (1993).
Pennica, D.et al. Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature 312, 724–729 (1984).
Pitti, R. M.et al. Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor receptor family. J. Biol. Chem. 271, 12687–12690 (1996).
Wiley, S. R.et al. Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3, 673–682 (1995).
Marsters, S. A.et al. Identification of a ligand for the death-domain-containing receptor Apo3. Curr. Biol. 8, 525–528 (1998).
Chicheportiche, Y.et al. TWEAK, a new secreted ligand in the TNF family that weakly induces apoptosis. J. Biol. Chem. 272, 32401–32410 (1997).
Wong, B. R.et al. TRANCE is a novel ligand of the TNFR family that activates c-Jun-N-terminal kinase in T cells. J. Biol. Chem. 272, 25190–25194 (1997).
Anderson, D. M.et al. Ahomolog of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature 390, 175–179 (1997).
Lacey, D. L.et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93, 165–176 (1998).
Dhein, J., Walczak, H., Baumler, C., Debatin, K. M. & Krammer, P. H. Autocrine T-cell suicide mediated by Apo1/(Fas/CD95). Nature 373, 438–441 (1995).
Arase, H., Arase, N. & Saito, T. Fas-mediated cytotoxicity by freshly isolated natural killer cells. J. Exp. Med. 181, 1235–1238 (1995).
Medvedev, A. E.et al. Regulation of Fas and Fas ligand expression in NK cells by cytokines and the involvement of Fas ligand in NK/LAK cell-mediated cytotoxicity. Cytokine 9, 394–404 (1997).
Moretta, A. Mechanisms in cell-mediated cytotoxicity. Cell 90, 13–18 (1997).
Tanaka, M., Itai, T., Adachi, M. & Nagata, S. Downregualtion of Fas ligand by shedding. Nature Med. 4, 31–36 (1998).
Gelmini, S.et al. Quantitative PCR-based homogeneous assay with fluorogenic probes to measure c-erbB-2 oncogene amplification. Clin. Chem. 43, 752–758 (1997).
Emery, J. G.et al. Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J. Biol. Chem. 273, 14363–14367 (1998).
Wallach, D. Placing death under control. Nature 388, 123–125 (1997).
Collota, F.et al. Interleukin-1 type II receptor: a decoy target for IL-1 that is regulated by IL-4. Science 261, 472–475 (1993).
Ashkenazi, A. & Dixit, V. M. Death receptors: signaling and modulation. Science 281, 1305–1308 (1998).
Ashkenazi, A. & Chamow, S. M. Immunoadhesins as research tools and therapeutic agents. Curr. Opin. Immunol. 9, 195–200 (1997).
Marsters, S.et al. Activation of apoptosis by Apo-2 ligand is independent of FADD but blocked by CrmA. Curr. Biol. 6, 750–752 (1996).
Acknowledgements
We thank C. Clark, D. Pennica and V. Dixit for comments, and J. Kern and P. Quirke for tumour specimens.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Pitti, R., Marsters, S., Lawrence, D. et al. Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature 396, 699–703 (1998). https://doi.org/10.1038/25387
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/25387
This article is cited by
-
Characterizing the regulatory Fas (CD95) epitope critical for agonist antibody targeting and CAR-T bystander function in ovarian cancer
Cell Death & Differentiation (2023)
-
A mathematical modeling technique to understand the role of decoy receptors in ligand-receptor interaction
Scientific Reports (2023)
-
A TRIM21-based bioPROTAC highlights the therapeutic benefit of HuR degradation
Nature Communications (2023)
-
Decoy receptor 3 is involved in epidermal keratinocyte commitment to terminal differentiation via EGFR and PKC activation
Experimental & Molecular Medicine (2022)
-
Serum decoy receptor 3 (DcR3): a promising biomarker for atopic asthma in children
Immunologic Research (2021)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
