Abstract
BackgroundTRAIL plays an important role in host immunosurveillance against tumor progression, as it induces apoptosis of tumor cells but not normal cells, and thus has great therapeutic potential for cancer treatment. TRAIL binds to two cell-death-inducing (DR4 and DR5) and two decoy (DcR1, and DcR2) receptors. Here, we compare the expression levels of TRAIL and its receptors in normal oral mucosa (NOM), oral premalignancies (OPM), and primary and metastatic oral squamous cell carcinomas (OSCC) in order to characterize the changes in their expression patterns during OSCC initiation and progression.MethodsDNA microarray, immunoblotting and immunohistochemical analyses were used to examine the expression levels of TRAIL and its receptors in oral epithelial cell lines and in archival tissues of NOM, OPM, primary and metastatic OSCC. Apoptotic rates of tumor cells and tumor-infiltrating lymphocytes (TIL) in OSCC specimens were determined by cleaved caspase 3 immunohistochemistry.ResultsNormal oral epithelia constitutively expressed TRAIL, but expression was progressively lost in OPM and OSCC. Reduction in DcR2 expression levels was noted frequently in OPM and OSCC compared to respective patient-matched uninvolved oral mucosa. OSCC frequently expressed DR4, DR5 and DcR1 but less frequently DcR2. Expression levels of DR4, DR5 and DcR1 receptors were not significantly altered in OPM, primary OSCC and metastatic OSCC compared to patient-matched normal oral mucosa. Expression of proapoptotic TRAIL-receptors DR4 and DR5 in OSCC seemed to depend, at least in part, on whether or not these receptors were expressed in their parental oral epithelia. High DR5 expression in primary OSCC correlated significantly with larger tumor size. There was no significant association between TRAIL-R expression and OSSC histology grade, nodal status or apoptosis rates of tumor cells and TIL.ConclusionLoss of TRAIL expression is an early event during oral carcinogenesis and may be involved in dysregulation of apoptosis and contribute to the molecular carcinogenesis of OSCC. Differential expressions of TRAIL receptors in OSCC do not appear to play a crucial role in their apoptotic rate or metastatic progression.
Highlights
tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plays an important role in host immunosurveillance against tumor progression, as it induces apoptosis of tumor cells but not normal cells, and has great therapeutic potential for cancer treatment
There were no significant differences in the expression levels of all three TRAIL receptors among normal, immortalized, premalignant, and malignant primary and metastatic oral epithelial cells (Figure 2)
There was no significant association between TRAIL-R expression and OSSC histology grade, nodal status, or apoptosis rates of tumor cells and tumor-infiltrating lymphocytes (TIL).Loss of TRAIL expression is an early event during oral carcinogenesis
Summary
TRAIL plays an important role in host immunosurveillance against tumor progression, as it induces apoptosis of tumor cells but not normal cells, and has great therapeutic potential for cancer treatment. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand; Apo2L) is a type II transmembrane protein which selectively induces apoptosis in tumor cells but not normal cells [1,2]. Because of this differential sensitivity TRAIL is considered an ideal anticancer drug [3,4]. Susceptibility to TRAIL-induced apoptosis does not always correlate well with the cell surface expression levels of death-inducing and decoy TRAIL receptors suggesting a regulatory role for downstream signaling and effector molecules [7,8]. Recent studies indicate that TRAIL susceptibility of tumors in vivo is modified by tumor microenvironmental factors and tumor hypoxia [9,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
