Effects of Extracellular Calcium on Cholesteatoma Migration and Adhesion in Vitro

Abstract

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.

Effect of trans-retinoic acid in the inhibition of cholesteatoma in guinea pigs

“…If calcium is removed from cholesteatoma growth and migration stimulating culture media, there is a tenfold reduction in the degree of cholesteatoma migration. 15 Calcium is essential for cell to cell adhesion, for instance, between keratinocytes and substrate cells. These authors studied the in vitro inhibitory effects of all-trans retinoic acid on cholesteatoma migration in human cholesteatoma samples cultured in cell-growth simulating media.…”

Effect of verapamil on cholesteatoma migration in vitro

“…The cells were then allowed to grow at 37°C in a humid atmosphere containing 5% carbon dioxide. Once growth and migration began, the rate of migration was measured (in millimeters) every 24 hours as previously described 7 . Migratory distances were determined by measuring the distance the center of each cell mass traveled every 24 hours.…”

Hystology findings' correlation between the ossicular chain in the transoperative and cholesteatomas

“…Ferlito et al 8 suggested that the destructive property of cholesteatomas, bone erosion, is caused by the collagenases produced by the components of squamous and fibrous epithelial tissues. The hypothesis of bone absorption by biochemical action exclusively done by collagenolitic enzimes was later incorporated by other agents, such as tumor necrosis factor (TNF), interleukins (IL-1a) and prostaglandins (PGE2) 9 , 10 , 11 .…”