Junctional Adhesion Molecule-C Mediates the Recruitment of Embryonic-Endothelial Progenitor Cells to the Perivascular Niche during Tumor Angiogenesis.

Autor: Czabanka M; Department of Neurosurgery, Universitätsmedizin Charitè, 10117 Berlin, Germany.; Department of Neurosurgery Medical Faculty of the University of Heidelberg, 68167 Mannheim, Germany., Petrilli LL; Department of Onco-haematology, Cell and Gene Therapy, Bambino Gesù Children's Hospital - IRCCS, 00146 Rome, Italy., Elvers-Hornung S; Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, German Fred Cross Blood Donor Service Baden-Württemberg - Hessen, 68167 Mannheim, Germany., Bieback K; Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, German Fred Cross Blood Donor Service Baden-Württemberg - Hessen, 68167 Mannheim, Germany., Albert Imhof B; Department of Pathology and Immunology, Medical Faculty, Centre Medical Universitaire (CMU), University of Geneva, 1206 Geneva, Switzerland., Vajkoczy P; Department of Neurosurgery, Universitätsmedizin Charitè, 10117 Berlin, Germany.; Department of Neurosurgery Medical Faculty of the University of Heidelberg, 68167 Mannheim, Germany., Vinci M; Department of Neurosurgery Medical Faculty of the University of Heidelberg, 68167 Mannheim, Germany.; Department of Onco-haematology, Cell and Gene Therapy, Bambino Gesù Children's Hospital - IRCCS, 00146 Rome, Italy.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2020 Feb 11; Vol. 21 (4). Date of Electronic Publication: 2020 Feb 11.
DOI: 10.3390/ijms21041209
Abstrakt: : 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.
Competing Interests: The authors declare that they have no competing interests.
Databáze: MEDLINE
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