Modulation of the terminal differentiation of human squamous carcinoma cells in vitro by all-trans-retinoic acid.
A malignant human cell line (SqCC/Y1) derived from a squamous carcinoma of the buccal mucosa is described. It formed a stratified cellular structure with ultrastructural characteristics of a fully differentiated stratified squamous epithelium when cultured in equal parts of Dulbecco's modified Eagle medium and Ham's medium F12, supplemented only with insulin, transferrin, and selenium. After 14 days in culture in this defined medium, 30% of the cells became keratinized (insoluble in detergent), and 75% of the cells were capable of being induced to form cornified cell envelopes. Involucrin, the precursor protein of the cornified cell envelope, could be detected by immunofluorescence only in suprabasal cells. Treatment of SqCC/Y1 cultures with 5 X 10(-8) M all-trans-retinoic acid (RA) completely inhibited stratification and markedly increased cell desquamation. In the presence of RA, less than 10% of the cells became keratinized, and only 15-20% of the cells acquired envelope-forming competence. The fraction of colony-forming cells in RA-treated cultures was tenfold higher than in fully mature cultures. Thus RA appears to be an effective inhibitor of terminal differentiation of SqCC/Y1 cells.
D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003470:Culture Media; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000502:physiology; D011498:Protein Precursors / Q000032:analysis; D014212:Tretinoin / Q000494:pharmacology*
D003470:Culture Media; D011498:Protein Precursors; D014212:Tretinoin; C032253:involucrin