Structural characterization of a fucoidan from Sargassum fusiforme and its antagonistic effect on T cell proliferation-inhibition induced by CAFs.

A water-soluble sulfated polysaccharide, SFAP-4, was isolated from Sargassum fusiforme via ion-exchange and gel-filtration column chromatography. It comprised a large amount of fucose (Fuc), minor amount of galactose (Gal), and small amounts of glucose (Glc), mannose (Man), rhammnose (Rha), xylose (Xyl) and glucuronic acid (GlcA). Structural analysis showed that SFAP-4 has very complex structure. It contains a backbone mainly consisted of →4)-α-L-Fucp-(1 → and →3)-α-L-Fucp-(1 → with different sulfated pattern in the ratio about 1:2. Most sulfate groups were disubstituted at O-2/4 of →3)-Fucp-(1 → and/or O-2/3 of →4)-Fucp-(1 → residues. Bioactivity tests showed that SFAP-4 restored T cell proliferation that was inhibited by cancer-associated fibroblasts (CAFs). SFAP-4 did not directly inhibit the apoptosis of CAFs, but it interfered with CAF-mediated T cell proliferation inhibition. The upregulated expression of pivotal proteins (p-p65 and p-TAK1) and NF-κB inhibitor blocking experiment indicated that the NF-κB pathway in CAFs was activated. Thus, SFAP-4 may antagonize against the T cell proliferation-inhibition induced by CAFs at least through the activation of the NF-κB pathway.