Glycosaminoglycans are anionic polysaccharides involved in the structure of the extracellular matrix. They function in growth control and probably the differentiation of epithelial cells, and are components of the intracellular cement and the adhesion plaques by which cells in culture contact the substratum. Alterations in the composition of the glycosaminoglycans occurs during development such that cells migrate in a milleu of loose connective tissue with predominantly hyaluronic acid, but differentiate in a matrix rich in sulfated glycosaminoglycans. Changes in the composition of these polysaccharides are also associated with tumors, and may show a pattern similar to that expected in developmentally immature tissues.
Our aim i s to compare the composition of the glycosaminoglycans of tissue during development, normal mature tissue, and tumors of the same tissue. The glycosaminoglycans of mouse mammary gland show the same pattern changes as developing organs during maturation from virgin glands to lactating, to retired breeders. The predominant hyaluronic of the virgin, or male, gland, becomes replaced with a series of heparans. The heparans so far isolated are unusually resistant to bacterial heparinitases. We propose to characterize these heparans by chemical degradation to the dissaccharides and analysis by chromatography and other chemical means to determine the specific structural features. Furthermore, the rates of turnover of the various components at each stage will be determined in vitro in the whole tissue. Preliminary data suggests that mammary tumors are indeed characterized by a more immature pattern of glycosaminoglycans. This will be further studied by examining the patterns obtained from the C3H mouse, which spontaneously develop mammary tumors. The compounds isolated from various stages of tumor development will be compared with the compounds from the normally developing gland. These studies will contribute to understanding the role of the extracellular matrix in determining tissue structure, and the mechanism by which tumors alter that structure to permit the malignant cells to invade the matrix. Such an understanding may ultimately suggest new approaches to cancer prevention and treatment.
| Umbreit, J N (1996) Modulation of glycosaminoglycans in mouse mammary tumors. Anticancer Res 16:3785-92 |
| Umbreit, J N (1996) Proteoglycans and glycosaminoglycans during maturation of the mouse mammary gland. Anticancer Res 16:3013-29 |
| Umbreit, J N (1996) A small RNA is associated with dermatan sulfate proteoglycan. Anticancer Res 16:1899-914 |
