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

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.

Biomaterials and Bioactive Natural Products from Marine Invertebrates: From Basic Research to Innovative Applications

“…In this framework, the specific biotechnological potential of the regular structure of echinoid fucoidans remains poorly investigated. However, it was shown that sulphated polysaccharides isolated from three sea urchin species have different anticoagulant and anti-selectin activities, which give them a potential activity in the attenuation of metastasis progression [245,246].…”

Cell-Free Coelomic Fluid Extracts of the Sea Urchin Arbacia lixula Impair Mitochondrial Potential and Cell Cycle Distribution and Stimulate Reactive Oxygen Species Production and Autophagic Activity in Triple-Negative MDA-MB231 Breast Cancer Cells

“…In conclusion, although the potential anti-cancer compounds obtained from echinoderms have been widely illustrated in the literature [49], the contribution of sea urchins to this field of research is still very limited and is represented only by a few pilot studies previously published and which focused on steroidal and polysaccharidic constituents [4,50,51]. Here, we have demonstrated the cytotoxicity of extracts from A. lixula's cell-free CF towards TNBC cells in vitro.…”

“…Sea urchins are invertebrates belonging to the class Echinoidea (phylum Echinodermata), which incorporates more than 700 described extant species worldwide. Recently, they have been the object of growing interest as available sources of new biomolecules which, on the basis of their activity as antibacterial, antiviral, antiprotozoal, antifungal, and anticancer agents, may be potential candidates for drug discovery and development [1][2][3][4]. Indeed, these animals have developed complex molecular mechanisms to use in various biological processes, such as communication, defense, reproduction, and antimicrobial resistance.…”

Sea cucumber Cucumaria frondosa fucoidan inhibits osteosarcoma adhesion and migration by regulating cytoskeleton remodeling

“…Their study revealed that Ups-fucoidan inhibited growth by downregulating VEGFC/VEGFR3, c-MET, cyclin D1, CDK4, PI3K/Akt and ERK, and suppressed adhesion and invasion by downregulating L-selectin and upregulating TIMPs. Similarly, other sulfated polysaccharides isolated from marine invertebrates (Strongylocentrotus droebachiensis and Echinometra lucunter) were revealed to attenuate tumor metastasis by a P-selectin-mediated mechanism (39). Another study (40) also demonstrated that Undaria pinnatifida fucoidan significantly inhibited the hypoxia-induced expression, nuclear translocation and activation of HIF-1α, the synthesis and secretion of VEGF-C and HGF, as well as the invasion and lymphatic metastasis in a mouse hepatocarcinoma Hca-F cell line.…”