TY - JOUR
T1 - Junctional adhesion molecule-C mediates the recruitment of embryonic-endothelial progenitor cells to the perivascular niche during tumor angiogenesis
AU - Czabanka, Marcus
AU - Petrilli, Lucia Lisa
AU - Elvers-hornung, Susanne
AU - Bieback, Karen
AU - Imhof, Beat Albert
AU - Vajkoczy, Peter
AU - Vinci, Maria
N1 - Funding Information:
This study was financially supported by grants of the European Union (FP7 ?Tumortargeting?) and the German Research Foundation (DFG SFR/TR23). Maria Vinci is a Children with Cancer UK Research Fellow. Acknowledgement: We are grateful to Elisabetta Dejana (Firc Institute of Molecular Oncology, Milan, Italy) for her kind gift of the H5V cell line.
Funding Information:
Funding: This study was financially supported by grants of the European Union (FP7 ’Tumortargeting’) and the German Research Foundation (DFG SFR/TR23). Maria Vinci is a Children with Cancer UK Research Fellow.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/2/2
Y1 - 2020/2/2
N2 - 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.
AB - 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.
KW - Adhesion
KW - Endothelial progenitors
KW - JAM-C
KW - Migration
KW - Perivascular niche
KW - Tumor angiogenesis
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U2 - 10.3390/ijms21041209
DO - 10.3390/ijms21041209
M3 - Article
C2 - 32054130
AN - SCOPUS:85079338327
VL - 21
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 4
M1 - 1209
ER -