Sulfated Fucan Inhibits Tumor Interaction With Endothelial Cells And Tumor Growth: Possible Contribution Of An Antivascular Endothelial Growth Factor (Vegf) Neutralizing Activity

The primary interaction between tumor and endothelial cells is mediated by endothelial selectins and sialyl-Lewis carbohydrates found on cancer cell surface. Heparin, a sulfated polysaccharide, binds to P- and L-selectins, an effect that has been associated with attenuation of metastasis. However, due to its strong anticoagulant activity, its use in anti-tumor therapy is restricted. Sulfated fucans from sea urchins have simple, unique structures of linear chains of sulfated α-L-fucose in well-defined repetitive patterns. In this study, we tested five sulfated fucans from different species of sea urchins for their ability to interfere with the tumor-endothelium interaction and compared our findings to those obtained with heparin. Our results show that sulfated fucan from L. variegatus (FucSulf I), bearing an unique 2,4-disulfated fucose residue and low anticoagulant activity, inhibits the adhesion of tumor cells to endothelium, tumor transendothelial migration and endothelial cell tubulogenesis, both by inhibiting P-selectin mediated tumor cell adhesion, and VEGF-dependent signaling in endothelial cells. FucSulf I also inhibited proliferation of several types of tumor cell lines in vitro and tumor growth in vivo . Our results indicate this sulfated fucan is a potential antitumor agent and a possible therapeutic alternative to heparin. Citation Format: Viviane Mignone, Camila Castro Figueiredo, Aline Oliveira, Eliene Kozlowski, Lubor Borsig, Mauro Pavao, Paulo Mourao, Veronica Morandi. Sulfated fucan inhibits tumor interaction with endothelial cells and tumor growth: Possible contribution of an antivascular endothelial growth factor (VEGF) neutralizing activity. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr B44.