Alteration in cholesteatoma fibroblasts: Induction of neoplastic-like phenotype

Cholesteatomas are invasive, locally destructive skin-like lesions that, after operative removal, have a significant recidivistic rate. These aggressive characteristics suggest a fundamental alteration in the biology of one or more of its constituents (i.e., keratinocytes, fibroblasts, and inflammatory cells). The cholesteatoma matrix was studied by subculturing it into its main cellular components. Short-term cell cultures of fibroblasts from cholesteatoma matrix and controls from ear canal and postauricular skin were established. These cultured fibroblasts were tested for invasiveness using the Boyden Chamber Assay of Albini. The cells were evaluated for their ability to migrate, attach to, and invade a basement membrane. Results of the motility and attachment of fibroblasts cultured from cholesteatoma, canal wall, and postauricular skin did not differ. However, fibroblasts from 12 of 12 cholesteatoma specimens were highly invasive, while those from postauricular and ear canal skin were either weakly invasive or not invasive. This represents the first report of an intrinsic defect in the biology of cholesteatoma. Invasive fibroblasts that demonstrate a loss of growth control, may provide a contact guidance mechanism that aggressively mobilizes the squamous keratinizing epithelium contributing to the invasive, aggressive behavior of cholesteatoma.