Glycosylation reactions and tumor establishment: modulation by vitamin A

The ability of retinoids to prevent or alter the course of experimental tumorigenesis is well established. We have extended these observations to include effects on establishment of tumors and tumor metastases. A diet containing excess retinyl acetate fed to rats prior to injection of a metastatic line of transplantable hepatoma, prevented establishment of secondary tumor foci while 75% of the animals fed adequate retinyl acetate showed pulmonary metastases. Metastatic ability may be related to the ability to bind fibronectins, proteins that link cells to an underlying stroma. Findings suggest involvement of higher gangliosides in the attachment of cells to a fibronectin-collagen complex. Prior to metastasis, hepatoma lines become depleted in the putative fibronectin receptor gangliosides as an end result of a complex cascade of altered glycosyltransferase activities. After metastasis, fibronectin receptors are apparently restored in those secondary tumor foci that become established. Analyses suggest that excess vitamin A may prevent the reappearance of fibronectin receptor gangliosides so that secondary tumor foci do not establish.