Proteoglycans and tumor progression: Janus-faced molecules with contradictory functions in cancer.
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.
Tímár
József
J
Department of Tumor Progression, National Institute of Oncology, Budapest, Hungary. jtimar@oncol.hu
Lapis
Károly
K
Dudás
József
J
Sebestyén
Anna
A
Kopper
László
L
Kovalszky
Ilona
I
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000473:pathology; D009369:Neoplasms / Q000378:metabolism* / Q000628:therapy; D011509:Proteoglycans / Q000378:metabolism*
D016326:Extracellular Matrix Proteins; D008562:Membrane Glycoproteins; D011509:Proteoglycans