Inhibitory effect of fucoidan on the adhesion of adenocarcinoma cells to fibronectin.
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-alpha5 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 alpha5 subunit and iii) by down-regulating the expression of vinculin.
Liu
Jian Miao
JM
Unité INSERM 428, Faculté de Pharmacie 4 avenue de l'Observatoire 75270 Paris, France.
Bignon
Jérôme
J
Haroun-Bouhedja
Ferial
F
Bittoun
Patrick
P
Vassy
Jany
J
Fermandjian
Serge
S
Wdzieczak-Bakala
Johana
J
Boisson-Vidal
Catherine
C
D000199:Actins / Q000378:metabolism; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D039482:Integrin alpha5 / Q000096:biosynthesis; D019012:Integrin beta1 / Q000096:biosynthesis; D011134:Polysaccharides / Q000378:metabolism / Q000494:pharmacology*
D000199:Actins; D000970:Antineoplastic Agents; D005353:Fibronectins; D039482:Integrin alpha5; D019012:Integrin beta1; D011134:Polysaccharides; C007789:fucoidan