首页|Effect of Eribulin on Angiogenesis and the Expression of Endothelial Adhesion Molecules
Effect of Eribulin on Angiogenesis and the Expression of Endothelial Adhesion Molecules
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NSTL
Int Inst Anticancer Research
Background/Aim: Tumor vasculature is an important component of the tumor microenvironment and deeply affects anticancer immune response. Eribulin is a nontaxane inhibitor of the mitotic spindle. However, off-target effects interfering with the tumor vasculature have been reported. The mechanisms responsible of this effect are still unclear. Materials and Methods: We designed an in vitro study to investigate the effect of eribulin, with or without TGF-/3, on neo-angiogenesis, and on the expression of the adhesion molecules ICAM-1 and VCAM-1. We also investigated the effects of paclitaxel and vinorelbine under the same experimental conditions. Results: Eribulin up-regulated the epithelial markers VE-cadherin and CD-31 in HUVEC and inhibited tube formation in HUVEC cells cultured in Matrigel. The drug effectively arrested tube formation even in the presence of TGF-/3 and counteracted the TGF-/3-induced change in cell shape from the endothelial cobblestone-like morphology to an elongated spindle-shaped morphology. We also observed that eribulin was able to upregulate ICAM-1 and to counteract its down-regulation induced by TGF-/3. Conclusion: Eribulin exerts different off-label effects: increases vascular remodeling, counteracts the endothelial-tomesenchymal transition (EndMT) mediated by TGF-/3 and promotes tumor infiltration by immune cells via increasing the expression of ICAM-1 and transcription of CD31 and VE cadherin. Moreover, eribulin was able to inhibit vasculature remodeling and the induction of EndMT mediated by TGF-/3 better than vinorelbine and paclitaxel. The effects observed in this study might have important therapeutic consequence if the drug is combined with immunotherapy.
NSTL
Int Inst Anticancer Research
