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Updated: Sep 21, 2025

In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing
Published on: May 11, 2021
Effect of Eribulin on Angiogenesis and the Expression of Endothelial Adhesion Molecules
Andrea Abbona1, Matteo Paccagnella1, Simonetta Astigiano2
1Translational Oncology Lab., ARCO Foundation, S. Croce & Carle Teaching Hospital, Cuneo, Italy.
Background/Aim:
Tumor vasculature is an important component of the tumor microenvironment and deeply affects anticancer immune response. Eribulin is a non-taxane 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-β, 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-β and counteracted the TGF-β-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-β.
Conclusion:
Eribulin exerts different off-label effects: increases vascular remodeling, counteracts the endothelial-to-mesenchymal transition (EndMT) mediated by TGF-β 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-β better than vinorelbine and paclitaxel. The effects observed in this study might have important therapeutic consequence if the drug is combined with immunotherapy.
Insights
Eribulin, a cancer drug, alters tumor blood vessels by inhibiting their growth and preventing harmful cell changes. These effects may enhance immunotherapy by promoting immune cell entry into tumors.
Area of Science:
- Oncology
- Cancer Biology
- Immunology
Background:
- Tumor vasculature significantly impacts the tumor microenvironment and anticancer immune responses.
- Eribulin, a non-taxane mitotic inhibitor, has reported off-target effects on tumor vasculature.
- The precise mechanisms behind eribulin's vascular effects remain unclear.
Purpose of the Study:
- To investigate eribulin's in vitro effects on neo-angiogenesis and adhesion molecule expression (ICAM-1, VCAM-1).
- To compare eribulin's vascular effects with paclitaxel and vinorelbine.
- To explore the influence of TGF-β on eribulin's vascular activity.
Main Methods:
- In vitro study design.
- Assessment of neo-angiogenesis and endothelial-to-mesenchymal transition (EndMT) markers.
- Analysis of ICAM-1 and VCAM-1 expression in response to eribulin, TGF-β, paclitaxel, and vinorelbine.
Main Results:
- Eribulin upregulated VE-cadherin and CD-31 in HUVECs and inhibited tube formation.
- Eribulin prevented TGF-β-induced changes in endothelial cell morphology and tube formation.
- Eribulin upregulated ICAM-1 and counteracted TGF-β-induced downregulation.
Conclusions:
- Eribulin promotes vascular remodeling and inhibits TGF-β-mediated EndMT.
- Eribulin enhances tumor infiltration by immune cells through increased ICAM-1 and CD31/VE-cadherin expression.
- Eribulin demonstrates superior inhibition of vasculature remodeling and EndMT compared to vinorelbine and paclitaxel, suggesting potential therapeutic synergy with immunotherapy.
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