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.

Anticancer Research
|May 31, 2022
PubMed
Abstract

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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