Figure 1.
Bortezomib counteracts cytokine-mediated upregulation of E-selectin, ICAM-1, and VCAM-1, but its anti-adhesive efficacy depends on the adhesive properties of the tumor cells
(A and B) E-selectin, ICAM-1, and VCAM-1 gene expression (A) and protein levels (B) in/on human umbilical vein endothelial cells (HUVEC) treated ± IL-1α, ± BZM. (C) Laminar flow adhesion assays were performed as illustrated to measure the anti-adhesive potential of BZM. (D) Number of flow-resistant adhesions of indicated tumor cell lines on ECs treated ± IL-1α, ± BZM. (E) Tumor-cell-surface expression levels of sialyl-Lewis A (sLeA) and sLeX. (F) Number of flow-resistant adhesions of indicated tumor cell lines on ECs treated with IL-1α ± E-selectin-blocking antibody. (G) Number and quality of adhesive events (legend in C) of indicated tumor cell lines on immobilized rhE-selectin under laminar flow conditions. (H) Tumor-cell-surface E-selectin binding capacity under static conditions. See Figure S1 for verification of these observations with multiple human tumor cell lines. Bar charts represent mean ± SD of n = 3; black lines in histograms represent isotype controls (B and E) and binding of human IgG1-Fc (H); ∗p < 0.05; n.s., not significant. Green indicates sLeA/X-positive tumor cell lines/models with BZM-resistant adhesion/metastasis, and blue indicates sLeA/X-negative tumor cell lines/models with BZM-sensitive adhesion/metastasis in all figures. Checked bars represent firm (flow-resistant) adhesions, open bars rolling adhesions, and striped bars tethering adhesions in all figures.