| Autor: |
Reale, Antonia, Carmichael, Irena, Xu, Rong, Mithraprabhu, Sridurga, Khong, Tiffany, Chen, Maoshan, Fang, Haoyun, Savvidou, Ioanna, Ramachandran, Malarmathy, Bingham, Nicholas, Simpson, Richard, Greening, David, Spencer, Andrew |
| Rok vydání: |
2021 |
| Předmět: |
|
| DOI: |
10.26181/604eb47ca7ae4 |
| Popis: |
"This is the peer reviewed version of the following article: Reale, A., Carmichael, I., Xu, R., et al. (2021). Human myeloma cell- and plasma-derived extracellular vesicles contribute to functional regulation of stromal cells. Proteomics, 21, e2000119. https://doi.org/10.1002/pmic.202000119 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions."Circulating small extracellular vesicles (sEV) represent promising non-invasive biomarkers that may aid in the diagnosis and risk-stratification of multiple myeloma (MM), an incurable blood cancer. Here, we comprehensively isolated and characterized sEV from human MM cell lines (HMCL) and patient-derived plasma (psEV) by specific EV-marker enrichment and morphology. Importantly, we demonstrate that HMCL-sEV are readily internalised by stromal cells to functionally modulate proliferation. psEV were isolated using various commercial approaches and pre-analytical conditions (collection tube types, storage conditions) assessed for sEV yield and marker enrichment. Functionally, MM-psEV were shown to regulate stromal cell proliferation and migration. In turn, pre-educated stromal cells favour HMCL adhesion. psEV isolated from patients with both pre-malignant plasma cell disorders (monoclonal gammopathy of undetermined significance [MGUS]; smouldering MM [SMM]) and MM have a similar ability to promote cell migration and adhesion, suggesting a role for both malignant and pre-malignant sEV in disease progression. Proteomic profiling of MM-psEV (305 proteins) revealed enrichment of oncogenic factors implicated in cell migration and adhesion, in comparison to non-disease psEV. This study describes a protocol to generate morphologically-intact and biologically functional sEV capable of mediating the regulation of stromal cells, and a model for the characterization of tumour-stromal cross-talk by sEV in MM. This article is protected by copyright. All rights reserved. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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