Langerhans' cell histiocytosis is caused by dysregulation of the E-cadherin-beta-catenin cascade: A hypothesis

Langerhans' cell histiocytosis (LCH) is a proliferative disease of cells of the dendritic cell lineage, closely resembling activated Langerhans' cells . The clinical picture of LCH is greatly variable, suggesting a scale of ab errancies at the cellular level. Despite progress in clinical treatment, th e aetiology and pathogenesis of this disease remain unknown. In the present paper, we present the hypothesis that dysregulation of the E-cadherin=beta -catenin-Wnt cascade, which has both adhesive and transcriptional functions , may be fundamental to the development of LCH. This hypothesis is founded upon two notions: (i) careful regulation of this cascade is essential in no rmal Langerhans cell activation; and (ii) abnormalities in the E-cadherin-b eta-catenin cascade are a major cause of epithelial neoplastic proliferatio n. On the basis of this hypothesis, we present three alternative scenarios that may describe the initial steps in the pathogenesis of LCH.