Activated platelet-derived exosomal LRG1 promotes multiple myeloma cell growth

Abstract The hypercoagulable state is a hallmark for patients with multiple myeloma (MM) and is associated with disease progression. Activated platelets secrete exosomes and promote solid tumor growth. However, the role of platelet-derived exosomes in MM is not fully clear. We aim to study the under...

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Published inOncogenesis (New York, NY) Vol. 13; no. 1; pp. 21 - 12
Main Authors Gao, Meng, Dong, Hang, Jiang, Siyi, Chen, Fangping, Fu, Yunfeng, Luo, Yanwei
Format Journal Article
LanguageEnglish
Published New York Nature Publishing Group 13.06.2024
Nature Publishing Group UK
Subjects
Angiogenesis
Apoptosis
Blood platelets
Cell growth
Cell proliferation
Exosomes
Flow cytometry
Immunofluorescence
Immunoprecipitation
Multiple myeloma
Olfactomedin
Peripheral blood
Platelets
Proteomes
Signal transduction
Solid tumors
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Summary:Abstract The hypercoagulable state is a hallmark for patients with multiple myeloma (MM) and is associated with disease progression. Activated platelets secrete exosomes and promote solid tumor growth. However, the role of platelet-derived exosomes in MM is not fully clear. We aim to study the underlying mechanism of how platelet-derived exosomes promote MM cell growth. Flow cytometry, Western blot, proteome analysis, co-immunoprecipitation, immunofluorescence staining, and NOD/SCID mouse subcutaneous transplantation model were performed to investigate the role of exosomal LRG1 on multiple myeloma cell growth. Peripheral blood platelets in MM patients were in a highly activated state, and platelet-rich plasma from MM patients significantly promoted cell proliferation and decreased apoptotic cells in U266 and RPMI8226 cells. Leucine-rich-alpha-2-glycoprotein 1 (LRG1) was significantly enriched in MM platelet-derived exosomes. Blocking LRG1 in recipient cells using LRG1 antibody could significantly eliminate the proliferation-promoting effect of platelet-derived exosomes on MM cells. And high exosomal LRG1 was associated with poor prognosis of patients with MM. Mechanistic studies revealed that LRG1 interacted with Olfactomedin 4 (OLFM4) to accelerate MM progression by activating the epithelial-to-mesenchymal transition (EMT) signaling pathway and promoting angiogenesis. Our results revealed that blocking LRG1 is a promising therapeutic strategy for the treatment of MM.
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ISSN:2157-9024
2157-9024
DOI:10.1038/s41389-024-00522-5