Effects of extracellular calcium on cholesteatoma migration and adhesion in vitro

Cholesteatoma matrix and tympanic epithelia share the unique property of en mass migratory locomotion in vitro. Although this migratory behavior is not well understood, it is thought to be a major contributor to the pathogenesis and pathophysiology of cholesteatoma disease. We have surmised that en mass migration depends on tight calcium-dependent intercellular and substrate cellular adhesions. The purpose of this investigation was to determine the effects of a diminished extracellular calcium level on cholesteatoma migration and adhesion. Cholesteatoma matrixes obtained intraoperatively from patients undergoing mastoidectomies for chronic ear disease were cut into small fragments and grown in culture. When cultured specimens were exposed to low-calcium medium (0.14 mmol/L calcium), a greater than 10-fold reduction in the rate of migration was observed when compared with control values (1.8 mmol/L calcium). This reduction of migration returned to normal within 48 hours after extracellular calcium was replenished. Substrate cellular adhesion was also significantly reduced when cholesteatoma cells were grown in low-calcium medium. These observations were further supported by histomorphologic findings. Our findings suggest that calcium-dependent intercellular and substrate cellular adhesions are essential for cholesteatoma migration and adhesion. These studies further our understanding of the pathophysiology of cholesteatoma disease and may provide clues on how to better treat patients with this disease.