Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation.
Irina Nazarenko,Sanyukta Rana,Alexandra Baumann,Jessica McAlear,Andrea Hellwig,Michael Trendelenburg,Günter Lochnit,Klaus T. Preissner,Margot Zöller +8 more
TLDR
EC uptake of Tspan8-CD49d complex-containing exosomes was accompanied by enhanced EC proliferation, migration, sprouting, and maturation of EC progenitors, which could provide new options for therapeutic interference with tumor-induced angiogenesis.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.read more
Citations
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Shedding light on the cell biology of extracellular vesicles.
TL;DR: Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material.
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Biogenesis, Secretion, and Intercellular Interactions of Exosomes and Other Extracellular Vesicles
TL;DR: Exosomes were described as vesicles of endosomal origin secreted from reticulocytes in the 1980s as discussed by the authors, and their biogenesis, their secretion, and their subsequent fate are discussed, as their functions rely on these important processes.
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Biological properties of extracellular vesicles and their physiological functions
María Yáñez-Mó,Pia Siljander,Zoraida Andreu,Apolonija Bedina Zavec,Francesc E. Borràs,Edit I. Buzás,Krisztina Buzas,Krisztina Buzas,Enriqueta Casal,Francesco Cappello,Joana Carvalho,Joana Carvalho,Eva Colas,Anabela Cordeiro da Silva,Anabela Cordeiro da Silva,Stefano Fais,Juan M. Falcón-Pérez,Irene M. Ghobrial,Bernd Giebel,Mario Gimona,Mario Gimona,Michael W. Graner,Ihsan Gursel,Mayda Gursel,Niels H. H. Heegaard,Niels H. H. Heegaard,An Hendrix,Peter Kierulf,Katsutoshi Kokubun,Maja Kosanović,Veronika Kralj-Iglič,Eva-Maria Krämer-Albers,Saara Laitinen,Cecilia Lässer,Thomas Lener,Thomas Lener,Erzsébet Ligeti,Aija Linē,Georg Lipps,Alicia Llorente,Jan Lötvall,Mateja Manček-Keber,Antonio Marcilla,María Mittelbrunn,Irina Nazarenko,Esther N. M. Nolte-‘t Hoen,Tuula A. Nyman,Lorraine O'Driscoll,Mireia Olivan,Carla Oliveira,Carla Oliveira,Éva Pállinger,Hernando A. del Portillo,Hernando A. del Portillo,Jaume Reventós,Jaume Reventós,Marina Rigau,Eva Rohde,Eva Rohde,Marei Sammar,Francisco Sánchez-Madrid,Nuno Santarém,Nuno Santarém,Katharina Schallmoser,Katharina Schallmoser,Marie Stampe Ostenfeld,Willem Stoorvogel,Roman Štukelj,Susanne G. van der Grein,M. Helena Vasconcelos,M. Helena Vasconcelos,Marca H. M. Wauben,Olivier De Wever +72 more
TL;DR: A comprehensive overview of the current understanding of the physiological roles of EVs is provided, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia.
Biogenesis, Secretion, and Intercellular Interactions of Exosomes and Other
TL;DR: The definition of exosomes and other secreted extracellular vesicles, which mediating intercellular communication between different cell types in the body, and thus affecting normal and pathological conditions are focused on.
Journal ArticleDOI
Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET
Héctor Peinado,Maša Alečković,Simon Lavotshkin,Irina Matei,Bruno Costa-Silva,Gema Moreno-Bueno,Marta Hergueta-Redondo,Caitlin Williams,Guillermo García-Santos,Cyrus M. Ghajar,Ayuko Nitadori-Hoshino,Caitlin Hoffman,Karen Badal,Benjamin A. Garcia,Margaret K. Callahan,Jianda Yuan,Vilma R. Martins,Johan Skog,Rosandra N. Kaplan,Mary S. Brady,Jedd D. Wolchok,Jedd D. Wolchok,Paul B. Chapman,Paul B. Chapman,Yibin Kang,Yibin Kang,Jacqueline Bromberg,Jacqueline Bromberg,David Lyden +28 more
TL;DR: The data show that exosome production, transfer and education of bone marrow cells supports tumor growth and metastasis, has prognostic value and offers promise for new therapeutic directions in the metastatic process.
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