Squamous cell differentiation markers in normal, premalignant, and malignant epithelium: effects of retinoids.

Vitamin A and some of its analogs (retinoids) maintain normal differentiation of epithelial tissues by preventing aberrant squamous differentiation of cells in nonkeratinizing epithelia. They can also reverse squamous metaplasia, which develops in vivo during vitamin A deficiency. These effects are the result of the ability of retinoids to suppress the expression of genes associated with squamous differentiation (e.g., transglutaminase type I, loricrin, involucrin, filaggrin, and keratin K1). In addition, retinoids reverse keratinizing premalignant lesions in the oral cavity, and inhibit the growth and squamous differentiation of head and neck squamous cell carcinomas (HNSCCs) in vitro. Nuclear retinoic acid receptors, which function as DNA-binding, trans-acting, transcription-modulating factors, are considered to be the proximate mediators of the effects of retinoids on gene expression and may mediate the re-regulation of aberrant differentiation and growth of premalignant and some malignant cells, thereby suppressing the development of head and neck cancer.