Inhibitory Effect of Fucoidan on the Adhesion of Adenocarcinoma Cells to Fibronectin

Abstract

Fucoidans inhibit tumour cell adhesion to various substrata, but their mechanisms of action are not fully understood. Using ³H-fucoidan, we observed that fucoidan binds to fibronectin, this binding being saturable and sensitive to ionic strength and pH. The interaction occurred on at least four different sites along the polypeptide chain, two of them being the heparin-binding sequences. Moreover, when MDA-MB-231 tumour cells were exposed to DTAF-fucoidan, internalization occurred and punctuated vesicles were observed in the perinuclear region. The treated cells also showed a different morphology with a cytoskeleton devoid of vinculin and a reorganiztion of the repartition of the integrin-α5 subunit on the cell surface. Based on these data, we hypothesize that fucoidan inhibits the adhesion of MDA-MB-231 cells to fibronectin i) by blocking the protein's heparin- and cell-binding domains, ii) by modulating the reorganization of the integrin α5 subunit and iii) by down-regulating the expression of vinculin.