Sulfated fucans and a sulfated galactan from sea urchins as potent inhibitors of selectin-dependent hematogenous metastasis

Glycobiology. 2018 Jun 1;28(6):427-434. doi: 10.1093/glycob/cwy020.

Abstract

Metastasis is responsible for the majority of cancer-associated deaths, though only a very small number of tumor cells are able to efficiently complete all the steps of that process. Tumor cell survival in the bloodstream is one of the limiting aspects of the metastatic cascade. The formation of tumor cell-platelet complexes that promote tumor cell survival is facilitated by the binding of P-selectin on activated platelets to sialyl Lewis-containing oligosaccharides on the surface of tumor cells. Inhibition of this interaction has been shown to attenuate metastasis. Heparin is a potent selectin inhibitor and is capable to block platelet-tumor cell complex formation, thereby attenuating metastasis. Similarly, other sulfated polysaccharides isolated from marine invertebrates attenuate metastasis by a P-selectin-mediated mechanism. In this work, we investigated the selectin-dependent antimetastatic activity of sea urchin sulfated polysaccharides with slight structural differences: a sulfated fucan from Strongylocentrotus franciscanus; a sulfated fucan from Strongylocentrotus droebachiensis; and a sulfated galactan from Echinometra lucunter. The results demonstrate that these fucans and the galactan have different antiselectin activities despite being very similar molecules. Therefore, they may be interesting tools for studies on the structure-function relationship or even for future treatments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Blood Platelets / drug effects
  • Cell Line, Tumor
  • Galactans / pharmacology
  • Galactans / therapeutic use*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Metastasis
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / pathology
  • Polysaccharides / pharmacology
  • Polysaccharides / therapeutic use*
  • Protein Binding
  • Sea Urchins / chemistry
  • Selectins / metabolism*

Substances

  • Antineoplastic Agents
  • Galactans
  • Polysaccharides
  • Selectins
  • fucoidan