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Protrusion‐guided extracellular vesicles mediate CD30 trans‐signalling in the microenvironment of Hodgkin's lymphoma
Author(s) -
Hansen Hinrich P,
Engels HannaMareike,
Dams Maria,
Paes Leme Adriana F,
Pauletti Bianca Alves,
Simhadri Vijaya Lakshmi,
Dürkop Horst,
Reiners Katrin S,
Barnert Sabine,
Engert Andreas,
Schubert Rolf,
Quondamatteo Fabio,
Hallek Michael,
Pogge von Strandmann Elke
Publication year - 2014
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4306
Subject(s) - microbiology and biotechnology , extracellular vesicle , ectodomain , cd30 , chemistry , vesicle , biology , microvesicles , immunology , receptor , biochemistry , lymphoma , microrna , membrane , gene
Classical Hodgkin's lymphoma ( cHL )‐affected lymphoid tissue contains only a few malignant Hodgkin and Reed–Sternberg ( HRS ) cells, which are disseminated within a massive infiltrate of reactive cells. In particular, the innate immune infiltrate is deemed to support tumour growth by direct cell–cell interaction. Since they are rarely found in close proximity to the malignant cells in situ , we investigated whether cHL ‐derived extracellular vesicles might substitute for a direct cell–cell contact. We studied the crosstalk of the transmembrane proteins CD30 and CD30 ligand ( CD30L ) because they are selectively expressed on HRS and innate immune cells, respectively. Here, we showed that HRS cells released both the ectodomain as a soluble molecule ( sCD30 ) and the entire receptor on the surface of extracellular vesicles. The vesicle diameter was 40–800 nm, as determined by cryo‐ and immune electron microscopy. In addition to CD30 , typical extracellular vesicle markers were detected by mass spectrometry and flow cytometry, including tetraspanins, flotillins, heat shock proteins and adhesion molecules. In contrast to sCD30 , vesicles caused a CD30 ‐dependent release of interleukin‐8 in CD30L + eosinophil‐like EoL ‐1 cells and primary granulocytes from healthy donors, underscoring the functionality of CD30 on vesicles. In extracellular matrix ( ECM )‐embedded culture of HRS cells, a network of actin and tubulin‐based protrusions guided CD30 + vesicles into the micro‐environment. This network targeted CD30 + vesicles towards distant immune cells and caused a robust polarization of CD30L . Confocal laser scanning microscopy of 30 µm sections showed a CD30 vesicle‐containing network also in cHL ‐affected lymphoid tissue of both mixed‐cellularity and nodular sclerosing subtypes. This network might facilitate the communication between distant cell types in cHL tissue and allow a functional CD30–CD30L interaction in trans . The tubulin backbone of the network may provide a target for the therapy of cHL with antitubulin‐based CD30 antibody constructs. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.