Effect of eribulin on angiogenesis and endothelial adhesion molecules.

Abstract

Tumor vasculature is an important component of the tumor microenvironment and deeply affect anticancer immune response. Eribulin is a non taxane inhibitor of the mitotic spindle. However, off-target effect interfering with the tumor vasculature have been reported. The mechanisms responsible of this effect is not clear. We designed an in vitro study to investigate the effect of eribulin on neo-angiogenesis and on the adhesion molecules ICAM-1 and VCAM-1, with or without TGF-{beta}. We also investigated the effects of paclitaxel and vinorelbine in the same experimental conditions. Eribulin was able to up-regulate the epithelial markers VE-cadherin and CD-31 in the HUVEC and tube formation in HUVEC cultured in Matrigel. The drug effectively arrested tube formation even in presence of TGF-{beta}. Eribulin counteracted the TGF-{beta} induced change in cell shape from the endothelial cobblestone-like morphology to an elongated spindle-shaped morphology that is characteristic of EndMT. We also observed that eribulin is able to upregulate ICAM-1 and to counteract its downregulation induced by TGF-{beta}. In this study, eribulin was able to inhibit the vasculature remodeling and the downregulation of ICAM-1 induced by TGF-{beta}. These effects might have important therapeutic consequence if the drug will be administered with immunotherapy.