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 beha vior is not well understood, it is thought to be a major contributor t o the pathogenesis and pathophysiology of cholesteatoma disease. We ha ve surmised that en mass migration depends on tight calcium-dependent intercellular and substrate cellular adhesions. The purpose of this in vestigation was to determine the effects of a diminished extracellular calcium level on cholesteatoma migration and adhesion. Cholesteatoma matrixes obtained intraoperatively from patients undergoing mastoidect omies 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 rare o f migration was observed when compared with control values (1.8 mmol/L calcium). This reduction of migration returned to normal within 48 ho urs after extracellular calcium was replenished. Substrate cellular ad hesion was also significantly reduced when cholesteatoma cells were gr own in low-calcium medium. These observations were further supported b y histomorphologic findings. Our findings suggest that calcium-depende nt intercellular and substrate cellular adhesions are essential for ch olesteatoma migration and adhesion. These studies further our understa nding of the pathophysiology of cholesteatoma disease and may provide clues on how to better treat patients with this disease.