Adhesive interactions between
selectins and their
ligands play an essential role during
cancer extravasation. Fucosylation of these
proteins by
fucosyltransferases, or FUTs, is critical for their functions. Using quantitative RT-PCR, we demonstrated that FUT4 and FUT7 are the predominant FUTs expressed in hematopoietic cell line, while FUT3 is heavily expressed by multiple
cancer cell lines including the
prostate cancer cell line MDA PCa2b. Knockdown of FUT3 expression in MDA PCa2b cells by small interference RNA (
siRNA) significantly reduced FUT3 expression. Cell-surface
sialyl Lewis antigens were largely abolished. Cell adhesion and cell rolling on the blood vessel wall were simulated by perfusing
cancer cells through microtubes coated with recombinant human
E-selectin. At physiological levels of wall shear stress, the number of flowing
cancer cells recruited to the microtube surface was dramatically reduced by FUT3 knockdown. Higher rolling velocity was also observed, which is consistent with reduced
E-selectin binding activity. Interestingly, FUT3
siRNA treatment also significantly reduced the cell growth rate. Combined with the novel
siRNA delivery platform recently developed in our laboratory, FUT3
siRNA could be a promising conjunctive
therapy aiming at reducing the metastatic virulence of circulating epithelial
cancer cells.