Expression of TRAIL and TRAIL receptors in normal and malignant tissues

Abstract

TRAIL, tumor necrosis factor-related apoptosis-inducing ligand, is a member of the TNF family of proteins. Tumour cells were initially found to have increased sensitivity to TRAIL compared with normal cells, raising hopes that TRAIL would prove useful as an anti-tumor agent. The production of reliable monoclonal antibodies against TRAIL and its receptors that can stain fixed specimens will allow a thorough analysis of their expression on normal and malignant tissues. Here we report the generation of monoclonal antibodies against TRAIL and its four membrane-bound receptors (TR1-4), which have been used to stain a range of normal and malignant cells, as routinely fixed specimens. Low levels of TRAIL expression were found to be limited mostly to smooth muscle in lung and spleen as well as glial cells in the cerebellum and follicular cells in the thyroid. Expression of the TRAIL decoy receptors (TR3 and 4) was not as widespread as indicated by Northern blotting, suggesting that they may be less important for the control of TRAIL cytotoxicity than previously thought. TR1 and TR2 expression increases significantly in a number of malignant tissues, but in some common malignancies their expression was low, or patchy, which may limit the therapeutic role of TRAIL. Taken together, we have a panel of monoclonal antibodies that will allow a better assessment of the normal role of TRAIL and allow assessment of biopsy material, possibly allowing the identification of tumors that may be amenable to TRAIL therapy.

TRAIL in the mandarin fish Siniperca chuatsi: Gene and its apoptotic effect in HeLa cells

“…The mRNA and protein of SCTRAIL gene are ubiquitously distributed in all examined tissues, which is similar to the pattern observed in the expression of TRAIL in mammals [9,10,25,32]. Although the expression of SCTRAIL at the level of mRNA and protein as revealed by RT-PCR and Western blotting cannot be considered as quantification, the strong bands observed in head kidney, spleen, kidney, and intestine may to some extent imply that SCTRAIL may have some role in fish immune system, but this speculation needs to be tested.…”

Super pH-sensitive multifunctional polymeric micelle for tumor pHe specific TAT exposure and multidrug resistance

“…The design of drug carriers targeting tumors have extensively exploited these paired cell-specific interactions (e.g., antigen/antibody and ligand/receptor) to target macromolecular or nanosized vehicles carrying cytotoxic drugs for internalization into tumor cells via intracellular delivery mediated by various active endocytotic pathways [3]. The repertoire of interactions for drug targeting is rather limited because solid tumors display rather heterogeneous cell populations as well as differential antigen or receptor expression on cell surfaces [4][5][6][7]. For example, HER2 antigen (human epidermal growth factor receptor 2 protein) currently used for breast tumor targeting is positive in only 20-30% of human breast tumor [4].…”

“…For example, HER2 antigen (human epidermal growth factor receptor 2 protein) currently used for breast tumor targeting is positive in only 20-30% of human breast tumor [4]. Moreover, normal cells often express the same antigens or receptors as do the tumor cells [5,6]. As an example, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been exploited for therapy since it induces apoptosis in tumor cells [5].…”

“…Moreover, normal cells often express the same antigens or receptors as do the tumor cells [5,6]. As an example, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been exploited for therapy since it induces apoptosis in tumor cells [5]. However, recent findings that healthy human hepatocytes, brain tissue, and certain epithelial cells are also susceptible to TRAIL have raised serious concerns of its potential toxicity if administered systemically [5].…”

SAHA/TRAIL combination induces detachment and anoikis of MDA-MB231 and MCF-7 breast cancer cells

“…TRAIL activates apoptosis upon binding to specific cell-surface death receptors (TRAIL-R1/DR4 and TRAIL-R2/DR5) in a wide variety of human tumor cell lines [10]. Moreover, TRAIL and some agonist antibodies are currently studied in patients in clinical phases I and II trials [11,12].…”