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Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation

Tumor-derived exosomes containing the tetraspanin Tspan8 can efficiently induce angiogenesis in tumors and tumor-free tissues. However, little information exists on exosome-endothelial cell (EC) interactions or the proangiogenic role of tetraspanins, which are a constitutive component of exosomes. I...

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Main Authors: Nazarenko, Irina (Author) , Rana, Sanyukta (Author) , Baumann, Alexandra (Author) , McAlear, Jessica (Author) , Hellwig, Andrea (Author) , Trendelenburg, Michael (Author) , Lochnit, Günter (Author) , Preissner, Klaus T. (Author) , Zöller, Margot (Author)
Format: Article (Journal)
Language:English
Published: 2/2/10
In: Cancer research
Year: 2010, Volume: 70, Issue: 4, Pages: 1668-1678
ISSN:1538-7445
DOI:10.1158/0008-5472.CAN-09-2470
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1158/0008-5472.CAN-09-2470
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Author Notes:Irina Nazarenko, Sanyukta Rana, Alexandra Baumann, Jessica McAlear, Andrea Hellwig, Michael Trendelenburg, Günter Lochnit, Klaus T. Preissner, and Margot Zöller
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Summary:Tumor-derived exosomes containing the tetraspanin Tspan8 can efficiently induce angiogenesis in tumors and tumor-free tissues. However, little information exists on exosome-endothelial cell (EC) interactions or the proangiogenic role of tetraspanins, which are a constitutive component of exosomes. In this study, we used a rat adenocarcinoma model (AS-Tspan8) to explore the effects of exosomal Tspan8 on angiogenesis. Tspan8 contributed to a selective recruitment of proteins and mRNA into exosomes, including CD106 and CD49d, which were implicated in exosome-EC binding and EC internalization. We found that EC internalized Tspan8-CD49d complex-containing exosomes. Exosome uptake induced vascular endothelial growth factor (VEGF)-independent regulation of several angiogenesis-related genes, including von Willebrand factor, Tspan8, chemokines CXCL5 and MIF, chemokine receptor CCR1, and, together with VEGF, VEGF receptor 2. EC uptake of Tspan8-CD49d complex-containing exosomes was accompanied by enhanced EC proliferation, migration, sprouting, and maturation of EC progenitors. Unraveling these new pathways of exosome-initiated EC regulation could provide new options for therapeutic interference with tumor-induced angiogenesis. Cancer Res; 70(4); 1668-78
Item Description:Gesehen am 08.05.2023
Physical Description:Online Resource
ISSN:1538-7445
DOI:10.1158/0008-5472.CAN-09-2470

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