1. Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation
- Author
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Andrea Hellwig, Margot Zöller, Sanyukta Rana, Jessica McAlear, Irina Nazarenko, Michael Trendelenburg, Günter Lochnit, Klaus T. Preissner, and Alexandra Baumann
- Subjects
CCR1 ,endocrine system ,Cancer Research ,Lung Neoplasms ,Angiogenesis ,Tetraspanins ,Biology ,Adenocarcinoma ,Exosomes ,Exosome ,chemistry.chemical_compound ,Chemokine receptor ,Tetraspanin ,Antigens, Neoplasm ,Animals ,RNA, Small Interfering ,Cells, Cultured ,Cell Proliferation ,Membrane Glycoproteins ,Neovascularization, Pathologic ,Cell Membrane ,Endothelial Cells ,Cell Differentiation ,Microvesicles ,Cell biology ,Neoplasm Proteins ,Rats ,Vascular endothelial growth factor ,Endothelial stem cell ,Gene Expression Regulation, Neoplastic ,Oncology ,chemistry ,Antigens, Surface ,Signal Transduction - Abstract
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
- Published
- 2010