Heparan Sulfate Proteoglycans Can Promote Opposite Effects on Adhesion and Directional Migration of Different Cancer Cells

Heparan sulfate proteoglycans take
part in crucial events of cancer
progression, such as epithelial–mesenchymal transition, cell
migration, and cell invasion. Through sulfated groups on their glycosaminoglycan
chains, heparan sulfate proteoglycans interact with growth factors,
morphogens, chemokines, and extracellular matrix (ECM) proteins. The
amount and position of sulfated groups are highly variable, thus allowing
differentiated ligand binding and activity of heparan sulfate proteoglycans.
This variability and the lack of specific ligands have delayed comprehension
of the molecular basis of heparan sulfate proteoglycan functions.
Exploiting a tumor-targeting peptide tool that specifically recognizes
sulfated glycosaminoglycans, we analyzed the role of membrane heparan
sulfate proteoglycans in the adhesion and migration of cancer cell
lines. Starting from the observation that the sulfated glycosaminoglycan-specific
peptide exerts a different effect on adhesion, migration, and invasiveness
of different cancer cell lines, we identified and characterized three
cell migration phenotypes, where different syndecans are associated
with alternative signaling for directional cell migration.