Retinoic acid inhibition of a head and neck multicellular tumor spheroid model.

The effects of retinoic acid (RA) on multicellular tumor spheroids (MTS) derived from a head and neck squamous carcinoma cell line, MDA 886Ln, were studied. Growth of MTSs was shown to be inhibited by 10(-5) to 10(-7) M RA; dose response studies demonstrated that by 10(-10) M RA, MTS growth was inhibited by less than 20%. MTSs treated with RA for 10 days had a decreased labeling index (15% compared with 23% for controls). Histologic studies at 10 days showed both an alteration in tissue-like architecture and an inhibition of squamous differentiation in RA-treated spheroids. Morphologic inhibition of differentiation was confirmed by immunohistochemical staining for involucrin. Histologic sections were also probed with a series of biotinylated lectins to search for RA-induced changes in glycosylation. Changes in staining occurred with two lectins, soybean agglutinin and peanut agglutinin. This study showed that RA induced perturbations in biological processes such as growth and differentiation in a new model system for squamous carcinomas of the head and neck, MDA 886Ln MTS.