Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer

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/Apol/CD95. 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 cells. 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.

Prognostic impact of FAS/CD95/APO-1 in urothelial cancers: decreased expression of Fas is associated with disease progression

“…Our results on FasL do not support the Fas -FasL tumour counterattack theory in UC. In addition, DcR3, a decoy receptor for FasL, drew attention as a new molecule working to evade activation of the Fas -FasL system (Pitti et al, 1998). In several other malignancies, DcR3 gene amplification and expression were reported (Roth et al, 2001;Mild et al, 2002).…”

“…Realtime PCR detection was performed in triplicate on the ABI Prism 7700 using a TaqMan instrument (Applied Biosystems, Tokyo, Japan) as previously described . DcR3 nucleotide sequences for primers are described previously (Pitti et al, 1998). To enable the standardisation of DNA quantity, TaqMan b-actin real-time PCR was performed for each sample, and the results were used to adjust the final results of real-time PCR for DcR3.…”

“…The validity of the Fas -FasL counterattack theory has been studied in several malignancies, and FasL expression could be a negative prognostic factor, such as in colorectal cancer (Mann et al, 1999;Okada et al, 2000). Second, decoy receptor 3 (DcR3) (TR6, M68), a decoy receptor for FasL, can play an important role in various cancers (Pitti et al, 1998;Roth et al, 2001). Moreover, recent study demonstrated that DcR3 expression might be a clinical marker in colorectal cancer (Mild et al, 2002).…”

Expression of TNFRSF6B in kidneys is a novel predictor for progression of chronic kidney disease

“…8 TNFRSF6B could act as decoy receptor to neutralize the proapoptotic effects of Fas ligand, LIGHT, and tumor necrosis factorlike molecule 1A by blocking the interaction with their respective receptors and evading immune surveillance. [8][9][10] Overexpression of TNFRSF6B, originally found in lung and colon cancers and virus-associated lymphoma, is capable of protecting cancer cells against apoptosis. 11 Mounting evidences have shown that TNFRSF6B overexpression is a novel tissue biomarker for predicting tumor invasion and worsening of various chronic inflammatory diseases.…”

In vitro and in vivo delivery of novel anticancer fusion protein MULT1E/FasTI via adenoviral vectors

“…11,12 One of the strategies that tumor cells have developed to escape NKG2D-mediated cytolysis by NK cells or cells expressing NKG2D is down-regulating NKG2D ligands such as MICA, 13,14 a process also called shedding. Tumor cells also escape Fas-mediated apoptosis by decreasing surface expression of Fas, 15,16 secreting an antagonistic 'decoy' receptor, 17 expressing anti-apoptotic molecules such as BCL2 family members, 17,18 down-regulating and mutating pro-apoptotic genes such as BAX, APAF1 or Fas. [19][20][21][22][23] In our earlier study 24 we combined the function of NKG2D-mediated cytolysis and Fas-mediated apoptosis into one functional fusion protein by using the extracellular domain of MULT1 and the transmembrane and intracellular domains of Fas in a mouse model.…”