TRAIL antibodies and their role in cancer research

Antibody suppliers have a wide range of reagents covering apoptosis

, or programmed cell death, including TRAIL (TNF-related apoptosis-inducing ligand) antibodies. TRAIL is of interest to cancer research groups as it is known to initiate programmed cell death in tumour cells.

TRAIL has several alternative names, including Apo2 ligand (Apo2L) and CD253 (cluster of differentiation 253). Its receptor interactions are just as complex. TRAIL binds to either the DR4 or DR5 death receptor, thus activating the caspase cascade and initiating programmed cell death. DR4 and DR5 are twin-domain proteins, consisting of a cytoplasmic TRAIL domain and a membrane-located death domain.

However, TRAIL also has 2 "decoy" receptors, DcR1 and DcR2. These do not initiate apoptosis. DcR1 lacks the cytoplasmic domain necessary for signalling to take place, and so works by neutralising TRAIL action. DcR2 lacks the truncated death domain, but has a functional cytoplasmic domain, known to activate NFkappaB following TRAIL binding. NFkappaB stimulates transcription of genes antagonistic to the death signalling pathway, and in some cases promotes an inflammatory response.

Recently, a third decoy receptor was discovered, DcR3. This inhibits apoptosis by binding to Fas ligand (FasL) and LIGHT protein, also known as TNFSF14. FasL and TRAIL are closely related, but whereas DcR1 and DcR2 are membrane associated, DcR3 is soluble and cytoplasmic.

TRAIL is expressed in a number of tissues, and is of interest to cancer research groups as the protein only induces apoptosis in altered cells, not normal ones. Following binding to DR4/5, caspase-8 dependent effector caspases are activated, leading to kinase activation and eventual cell death. Early studies were concentrated on overexpression of TRAIL in tumour cells. However, more recent antibody studies have concentrated on the apoptotic signalling pathways and decoy receptors, which are known to play a role in carcinoma formation. We at Novus Biologicals have a large antibody database covering the full spectrum of apoptosis proteins.

TRAIL antibodies and their role in cancer research

By: Ronald Kresten

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