Inhibition of cholesteatoma migration in vitro with all-trans retinoic acid

Retinoids have recently become of interest to clinicians because of their ability to inhibit migration and proliferation of premalignant squamous cells while enhancing growth and proliferation of normal cells. An in vitro investigation was undertaken to determine whether retinoic acid exhibits similar inhibitory effects on cholesteatoma cells. Cholesteatoma specimens were obtained intraoperatively from 10 patients undergoing mastoidectomy or revision mastoidectomy for chronic ear disease. Cholesteatoma explant growth and en mass migration were observed daily, and topographic maps were constructed at various time intervals to quantity rate and direction of explant migration in the presence or absence of all-trans retinoic acid. Before all-trans retinoic acid administration, explants migrated very rapidly (1 to 2 mm/day). A maximum threefold inhibition of migratory rate occurred, with explants exposed to 0.1 micromol/L retinoic acid when compared with controls. A sixfold maximum inhibition was observed at higher retinoic acid concentrations (5 micromol/L). On removal of all-trans retinoic acid, twofold and fourfold increases in migratory rates were observed. The direction of explant migration varied significantly for long periods of time and appeared not to be affected by retinoic acid. This investigation suggests that all-trans retinoic acid has an inhibitory effect on cholesteatoma cell migration. Retinoids may have a role in controlling cholesteatoma disease in the future.