Aims and background: The receptor for advanced glycation end products (RAGE) is a multiligand cell surface receptor of the immunoglobulin superfamily and a newly recognized invasion-related gene. High mobility group box-1 (HMGB-1) is a 30-kD protein binding to RAGE and acting as a transcription-factor-like protein that regulates the expression of several genes. In this study, the interaction effect between RAGE and HMGB-1 on the migration of SCC7 cells was investigated along with the inhibitory effect of the drug nifedipine on this interaction effect.
Methods and study design: Ten surgical specimens from patients with squamous cell carcinoma (SCC) of the head and neck and a SCC7 cell line were stained using immunohistochemical and immunocytochemical methods. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect RAGE expression in SCC7 cells; Western blot analysis was used to detect HMGB-1 expression in SCC7 cells. An in vitro migration assay (Boyden chamber migration assay) was used for evaluating the interaction effect between RAGE and HMGB-1 on the migration of SCC7 cells. HMGB-1 and various concentrations of nifedipine were tested for their effect on SCC7 cell migration with in vitro migration assays.
Results and conclusions: RAGE and HMGB-1 were expressed in almost all human head and neck SCC tissues and in SCC7 cells as detected by immunostaining. The migration assay showed that the interaction between RAGE and HMGB-1 increased SCC7 migration activity depending on the level of HMGB-1, and nifedipine inhibited the interaction effect between RAGE and HMGB-1 on SCC7 cells in a dose-dependent manner. The interaction between RAGE and HMGB-1 could be closely associated with metastasis of SCC of the head and neck. Nifedipine may have an inhibitory effect on tumor metastasis.