Junctional adhesion molecule-C mediates the recruitment of embryonic-endothelial progenitor cells to the perivascular niche during tumor angiogenesis

Marcus Czabanka, Lucia Lisa Petrilli, Susanne Elvers-hornung, Karen Bieback, Beat Albert Imhof, Peter Vajkoczy, Maria Vinci

Research output: Contribution to journalArticlepeer-review

Abstract

The homing of Endothelial Progenitor Cells (EPCs) to tumor angiogenic sites has been described as a multistep process, involving adhesion, migration, incorporation and sprouting, for which the underlying molecular and cellular mechanisms are yet to be fully defined. Here, we studied the expression of Junctional Adhesion Molecule-C (JAM-C) by EPCs and its role in EPC homing to tumor angiogenic vessels. For this, we used mouse embryonic-Endothelial Progenitor Cells (e-EPCs), intravital multi-fluorescence microscopy techniques and the dorsal skin-fold chamber model. JAM-C was found to be expressed by e-EPCs and endothelial cells. Blocking JAM- C did not affect adhesion of e-EPCs to endothelial monolayers in vitro but, interestingly, it did reduce their adhesion to tumor endothelium in vivo. The most striking effect of JAM-C blocking was on tube formation on matrigel in vitro and the incorporation and sprouting of e-EPCs to tumor endothelium in vivo. Our results demonstrate that JAM-C mediates e-EPC recruitment to tumor angiogenic sites, i.e., coordinated homing of EPCs to the perivascular niche, where they cluster and interact with tumor blood vessels. This suggests that JAM-C plays a critical role in the process of vascular assembly and may represent a potential therapeutic target to control tumor angiogenesis.

Original languageEnglish
Article number1209
JournalInternational Journal of Molecular Sciences
Volume21
Issue number4
DOIs
Publication statusPublished - Feb 2 2020

Keywords

  • Adhesion
  • Endothelial progenitors
  • JAM-C
  • Migration
  • Perivascular niche
  • Tumor angiogenesis

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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