The Expression Of TRAIL And TRAILR Protein In Tumor Tissues And Relationship With Blastoderm

In recent years, many new members of the tumor necrosis factor (TNF) ligand and receptor superfamilies have been identified, but none of these molecules has attracted more attention than TNF-related apoptosis inducing ligand (TRAIL) and its receptors. TRAIL was discovered by two independent groups, Wiley and Pitti et al. The role of TRAIL in tumor therapy becomes popular recently, because TRAIL could induce apoptosis in cancer cell lines. TRAIL is expressed as a typeâ…¡membrane protein of about 32.5 kDa. The primary structure of this protein contains 281 amino acids with an N-terminal cytosolic domain of 14 residues that precedes a stretch of 26 hydrophobic residues characteristic of typeâ…¡transmembrane protein. TRAIL is detected in a wide variety of tissues. It educes different effect by binding its receptors. The extracellular domain of TRAIL forms a homotrimer, much like other ligands of the TNF family.There are five distinct receptors, death receptor 4 (DR4), DR5, decoy receptor 1 (DcR1), DcR2, and OPG (osteoprotegerin ), for TRAIL ligand. DR4 and DR5 exhibit significant homology with each other (58% identity). Among them DR4 and DR5 contain death domains (DD) in their cytoplasmic region and can mediate cell apoptosis upon ligation with membrane form TRAIL or soluble TRAIL. In contrast, DcR1 and DcR2 contain no DD or incomplete death domain lacking the ability to induce apoptotic signal and have been hypothesized as protective receptors, either by acting as"decoy"receptors or via transduction of an antiapoptotic signal.The recombinant soluble TRAIL induces apoptosis in a broad spectrum of human cancer cell lines, including colon, lung, breast, prostate, pancreas, kidney, central nervous system and thyroid cancer cells, as well as multiple myeloma, melanoma and osteosarcoma . Similarly, administration of recombinant soluble TRAIL to SCID mice, that bear human tumor xenografts derived from colon and breast carcinomas, multiple myeloma or malignant glioma, exerted marked anti-tumor activity without systemic toxicity .Several reports studied the mRNA expression of TRAIL and its receptors in a variety of malignant tissues. It is becoming increasingly clear that mRNA expression of TRAIL receptors is not a reliable indicator of the expression of the proteins on the cell surface, so the true importance of the decoy receptors in determining sensitivity is still unclear. A few tissues revealed no detectable protein, although mRNA expression had been described earlier. Immunohistochemical staining is a better technique to study in more detail which cells express the protein of interest. In this study the protein expression of TRAIL, DR4, DR5, DcR1 and DcR2 in 10 common tumor tissues was investigated by immunohistochemical staining. The relationship between distribution and blastoderm of these tumor tissues was analyzed.The results showed that the expression of TRAIL decreased from normal rectal mucosa, surrounding tissues to rectal cancer, while the expression of DR4 and DR5 was opposite. The expression of DR5 was stronger. The expression of DcR was higher in poor differentiation degree of rectal cancer, however, its level was lower in high differentiation degree.Our study also revealed that TRAIL, DR4, DR5, DcR1 and DcR2 expressed in nasopharynx, larynx, breast, prostate, kidney, liver, stomach, colon, rectum and thyroid tumor tissues. But their expression level was relatively lower in prostate and kidney tumor tissues The expression of TRAIL and TRAILR had no difference between the tumor tissues derived from ectoderm and endoderm (P>0.05). However, the expression of TRAIL and TRAILR in tumor tissues of ectoderm and endoderm was higher than that of mesoderm (P<0.05). These results suggested that the expression of TRAIL and TRAILR has a close relationship with the origin of tumor, which provids insights in the efficacy and the possible adverse effects, clinical studies may also lead to an even more profound apprehension of the TRAIL-pathway and may give rise to true tumour-tailored therapy by combining knowledge on the TRAIL signalling pathway with clinical response data and tumour characteristics.To ascertain the apoptosis in cancer cells, the apoptosis was measured by TUNEL staining. The study exhibited TRAIL could induce apoptosis in nasopharynx, larynx, breast, prostate, kidney, liver, stomach, colon, rectum and thyroid tumor tissues, while it bound its receptors. The apoptosis rate in cancer cells of ectoderm and endoderm was higher than that of mesoderm. TUNEL staining revealed the apoptosis number was rather lower than that of the result of immunohistochemical staining. The result hinted the relationship between the distribution of TRAIL /TRAILR and the tissues origin. Membrane bound TRAIL might be a main form in inducing apoptosis. The molecule principle of TRAIL in inducing apoptosis is still unclear, so more research should have to be done.