Figure 3.

The anti-adhesive and anti-metastatic effects of BZM depend on E-selectin, and the endothelial adhesion strength depends on the tumor cells' E-selectin ligand statuses

(A and B) Number and quality of dynamic adhesions of indicated tumor cell lines on ECs after cytokine-stimulation ± ICAM-1 (A) or VCAM-1 blockade (B). (C) E-selectin, ICAM-1, and VCAM-1 cell-surface protein expression on ECs (treated ± IL-1α ± BZM) after stable (shRNA-mediated) depletion of E-selectin or control transduction. (D) Number of flow-resistant adhesions of indicated tumor cell lines on control or E-selectin-depleted ECs, treated ± IL-1α ± BZM. (E) s.c. HOS xenograft primary tumor growth periods and tumor weights as well as spontaneous lung metastasis numbers at necropsy in PBS- (control) or BZM-treated Sele^−/- SCID mice. This treatment was carried out as in Figures 2A and 2B. The effect on the tumor growth period was considered as a covariate in the statistical analysis of lung metastasis numbers (ANCOVA). (F) Stability of endothelial adhesions of indicated tumor cell lines on cytokine-stimulated ECs. (G) Maximum adhesion force required for retracting single tumor cells of the indicated cell lines from control versus cytokine-stimulated ECs. Bar charts represent mean ± SD of n = 3 (A, B, and D) and n ≥ 3 (G); ∗p < 0.05.