Single-molecule force spectroscopy reveals structural differences of heparan sulfate chains during binding to vitronectin.

The syndecans represent an ongoing research field focused on their regulatory roles in normal and pathological conditions. The role of syndecans in cancer progression is well documented, implicating their importance in diagnosis and even proposing various potential cancer treatments. Thus, the characterization of the unbinding properties at the single-molecule level will appeal to their use as targets for therapeutics. In our study, syndecan-1 and syndecan-4 were measured during the interaction with the vitronectin HEP II binding site. Our findings show that syndecans are calcium ion dependent molecules that reveal distinct, unbinding properties indicating the alterations in the structure of heparan sulfate (HS) chains, possibly in the chain sequence or sulfation pattern. In this way, we suppose that HS chain affinity to extracellular matrix proteins may govern cancer invasion by altering the syndecans' ability to interact with cancer-related receptors present in the tumor microenvironment, thereby promoting the activation of various signaling cascades regulating tumor cell behavior.