Retinoids and tumorigenesis: mechanistic considerations.
Retinoids enhanced adhesion of spontaneously-transformed mouse fibroblasts to the substrate of culture in a reversible way. They also caused an increase in the incorporation of radioactively-labeled mannose into 'complex type' oligosaccharides of glycopeptides isolated from the cell surface. Consistent with this response was a similar increase in 'complex type' oligosaccharide chains from the collagen binding domain of fibronectin from retinoid-treated, more adhesive rat sternal chondrocytes. Tumor promoting phorbol esters caused a decrease in adhesion and the shedding of fibronectin from the cell surface. Opposing actions of tumor promoting agents and retinoids exist at the level of expression of squamoid metaplasia of the respiratory tract. Both hepatomas with minimal and a maximal growth rate contained less retinyl palmitate than host liver. Similarly, the level of the cellular retinol binding protein (CRBP) was greatly reduced in the hepatoma tissue. Considerations on the antagonistic actions of tumor promoters and retinoids, the phenotype of squamous cell carcinomas of the bronchus and the vitamin A deficient status of hepatoma tissue suggested the following concepts: compounds which perform essential functions (e.g. vitamin A) may prevent initiated cells from expressing the tumorigenic phenotype; tumor promoters may act by interfering either directly or indirectly with the essential function of these compounds; normal cells respond to deficiency of essential function by differentiation and/or cell death; and initiated cells express the new phenotype, have a growth advantage and become self-sufficient.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control*; D012176:Retinoids / Q000378:metabolism / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D014801:Vitamin A / Q000378:metabolism; D014802:Vitamin A Deficiency / Q000150:complications
D002273:Carcinogens; D012176:Retinoids; D014801:Vitamin A; D013755:Tetradecanoylphorbol Acetate