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Proteoglycans and tumor progression:: Janus-faced molecules with contradictory functions in cancer

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SEMINARS IN CANCER BIOLOGY
卷 12, 期 3, 页码 173-186

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ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/S1044-579X(02)00021-4

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proteoglycan; glycosaminoglycan; invasion; metastasis; diagnosis; therapy

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Understanding the details of the molecular mechanism of tumor dissemination revealed that several proteoglycan species are involved in the process but their role can be described as janus-faced. On level of proteoglycan alterations is at the expression of their genes coding for the core protein. Characteristically, in Progressing tumors two patterns emerged: loss or neoexpression of surface proteoglycans (PG) depending on the initial expression pattern of the cell type of origin. The situation is similarly complex concerning the changes of glycosaminoglycan (GAG) of the, PC; during tumor progression. This is due to the fact that the majority of PGs involved is hybrid molecule meaning that their cow protein can be glycanated both with chondroitin and heparan sulfate. However, such an alteration in g vcanation of PG may fundamentally change the function of the molecule, especially the one operating at the, cell surface. Among the extracellular PGs, decorin emerged as inhibitor of progression while perlecan as a promoter of the process. Analysis of the available data indicate that during metastatization tumor cells must express at least one cell surface HSPC pecies from the syndecan-glypican-CD44v3 group. Furthermore, the HS-chain of these proteoglycan(s) carry important molecular signatures (suphution or epimerization Patterns). Experimental data suggest that tumor cell surface heparan sulfate (PG) may provide a target for specific anti-metastatic interventions.

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