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Effects of Retinoic Acid on Morphological Features and Biological Markers of a Neoplastic Human Salivary Intercalated Duct Cell Line in Culture¹

Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, 3 Kuramoto-cho, Tokushima 770, Japan

Retinoic acid has marked effects on the growth, morphological features, and biological markers of a neoplastic human salivary intercalated duct cell clone in culture, whereas the cell clone was not affected by other retinoids such as retinol and retinal. A cell clone with ultrastructure and biological markers specific to the intercalated duct cells of human salivary glands was cultivated in the presence of retinoic acid. Major alterations, such as expression of tonofilaments, M_r 68,000 cytokeratin, and involucrin, were observed in those cells with a phenotype similar to that of keratinizing squamous cells. In addition, the coexpression of M_r 68,000 cytokeratin and carcinoembryonic antigen in these altered cells was found. Both the anchorage-independent and anchorage-dependent growths were markedly suppressed in the presence of retinoic acid. After the removal of retinoic acid from the culture, the treated cells returned rapidly to the phenotype of the untreated cells. These findings indicate that reversible differentiation into the keratinizing squamous cells of a neoplastic human salivary intercalated duct cell clone occurs in growth medium containing retinoic acid.

¹ This investigation was supported in part by Grant-in-Aid for Scientific Research 61440083, from the Ministry of Education, Science and Culture of Japan.

² To whom requests for reprints should be addressed.

Received 2/16/88. Revised 6/29/88. Revised 9/ 6/88. Accepted 9/16/88.