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dc.contributor.authorStrømme, Olaf
dc.contributor.authorPsonka Antonczyk, Katarzyna Maria
dc.contributor.authorStokke, Bjørn Torger
dc.contributor.authorSundan, Anders
dc.contributor.authorArum, Carl-Jørgen
dc.contributor.authorBrede, Gaute
dc.identifier.citationExperimental Cell Research. 2019, 383 (1), .nb_NO
dc.description.abstractMultiple myeloma is an incurable cancer of antibody-producing plasma cells. Hepatocyte growth factor (HGF), a cytokine aberrantly expressed in half of myeloma patients, is involved in myeloma pathogenesis by enhancing myeloma growth and invasiveness, and may play a role in myeloma bone disease by inhibiting osteoblastogenesis. In this study, we investigated whether extracellular vesicles (EVs) may play a role in HGF signaling between myeloma cells and osteoblast-like target cells. EVs from the HGF-positive cell line JJN-3 and the HGF-negative cell line INA-6, and from bone marrow plasma and primary human myeloma cells, were isolated using sequential centrifugation techniques and the presence of HGF on the EV-surface was investigated with ELISA. EVs from both cell lines were added to an established bioassay where HGF is known to induce interleukin-11 secretion in osteoblast-like cells. Our results show that HGF was bound to the surface of JJN-3-derived EVs, while INA-6-derived EVs were negative for HGF. Only JJN-3-derived EVs induced IL-11 secretion in osteoblast-like recipient cells. When osteoblast-like cells were preincubated with a specific HGF-receptor (c-Met) inhibitor, no induction of interleukin-11 was observed. Downstream c-Met phosphorylation was demonstrated by immunoblotting. EVs isolated from bone marrow plasma and primary myeloma cells were HGF-positive for a subset of myeloma patients. Taken together, this work shows for the first time that HGF bound on the surface of myeloma-derived EVs can effectuate HGF/c-Met signaling in osteoblast-like cells. Myeloma-derived EVs may play a role in myeloma bone disease by induction of the osteoclast-activating cytokine interleukin-11 in osteoblasts.nb_NO
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internasjonal*
dc.titleMyeloma-derived extracellular vesicles mediate HGF/c-Met signaling in osteoblast-like cellsnb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.source.journalExperimental Cell Researchnb_NO
dc.description.localcode© 2019. This is the authors’ accepted and refereed manuscript to the article. Locked until 5.7.2020 due to copyright restrictions. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
cristin.unitnameInstitutt for klinisk og molekylær medisin
cristin.unitnameInstitutt for fysikk
cristin.unitnameKirurgisk klinikk

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Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal
Med mindre annet er angitt, så er denne innførselen lisensiert som Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal