In vitro modulation of human laryngeal papilloma cell differentiation by retinoic acid.

We have defined conditions permitting the in vitro growth of human laryngeal papilloma cells at the air-liquid interface. Using this model system, retinoic acid has been found to modulate the differentiation of human laryngeal papilloma cells along two different pathways. At low concentrations of retinoic acid [10(-9) mol/L and 10(-8) mol/L], the cells formed a stratified squamous epithelium with a differentiation-specific protein staining pattern identical to that found in vivo. At higher concentrations of retinoic acid [10(-7) mol/L and 10(-6) mol/L], the cells differentiated into a columnar epithelium with occasional ciliated cells, lacking the markers of squamous differentiation. Analysis of the human papillomavirus DNA content revealed that as the concentration of retinoic acid increased, the viral DNA content decreased. This system is proposed as a model to further investigate the differentiation defects of human laryngeal papilloma cells and the regulatory role of retinoic acid in the clinical expression of human laryngeal papillomatosis.