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. One 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 PG during tumor progression.
This is due to the fact that the majority of PGs involved is hybrid molecule meaning
that their core protein can be glycanated both with chondroitin and heparan sulfate.
However, such an alteration in glycanation 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 HSPG species 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.
