Analysis of Amount, Size, Protein Phenotype and Molecular Content of Circulating Extracellular Vesicles Identifies New Biomarkers in Multiple Myeloma.


Journal

International journal of nanomedicine
ISSN: 1178-2013
Titre abrégé: Int J Nanomedicine
Pays: New Zealand
ID NLM: 101263847

Informations de publication

Date de publication:
2021
Historique:
received: 25 01 2021
accepted: 11 03 2021
entrez: 17 5 2021
pubmed: 18 5 2021
medline: 25 5 2021
Statut: epublish

Résumé

Extracellular vesicles (EVs) are naturally secreted cellular lipid bilayer particles, which carry a selected molecular content. Owing to their systemic availability and their role in tumor pathogenesis, circulating EVs (cEVs) can be a valuable source of new biomarkers useful for tumor diagnosis, prognostication and monitoring. However, a precise approach for isolation and characterization of cEVs as tumor biomarkers, exportable in a clinical setting, has not been conclusively established. We developed a novel and laboratory-made procedure based on a bench centrifuge step which allows the isolation of serum cEVs suitable for subsequent characterization of their size, amount and phenotype by nanoparticle tracking analysis, microscopy and flow cytometry, and for nucleic acid assessment by digital PCR. Applied to blood from healthy subjects (HSs) and tumor patients, our approach permitted from a small volume of serum (i) the isolation of a great amount of EVs enriched in small vesicles free from protein contaminants; (ii) a suitable and specific cell origin identification of EVs, and (iii) nucleic acid content assessment. In clonal plasma cell malignancy, like multiple myeloma (MM), our approach allowed us to identify specific MM EVs, and to characterize their size, concentration and microRNA content allowing significant discrimination between MM and HSs. Finally, EV associated biomarkers correlated with MM clinical parameters. Overall, our cEV based procedure can play an important role in malignancy biomarker discovery and then in real-time tumor monitoring using minimal invasive samples. From a practical point of view, it is smart (small sample volume), rapid (two hours), easy (no specific expertise required) and requirements are widely available in clinical laboratories.

Identifiants

pubmed: 33994784
doi: 10.2147/IJN.S303391
pii: 303391
pmc: PMC8114829
doi:

Substances chimiques

Biomarkers, Tumor 0
MicroRNAs 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

3141-3160

Informations de copyright

© 2021 Laurenzana et al.

Déclaration de conflit d'intérêts

The authors report no conflicts of interest in this work.

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Auteurs

Ilaria Laurenzana (I)

Laboratory of Preclinical and Translational Research, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, PZ, Italy.

Stefania Trino (S)

Laboratory of Preclinical and Translational Research, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, PZ, Italy.

Daniela Lamorte (D)

Laboratory of Preclinical and Translational Research, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, PZ, Italy.

Marco Girasole (M)

Institute for the Study of the Structure of Matter, National Research Council (CNR), Rome, Italy.

Simone Dinarelli (S)

Institute for the Study of the Structure of Matter, National Research Council (CNR), Rome, Italy.

Angelo De Stradis (A)

Institute for Sustainable Plant Protection, National Research Council (CNR), Bari, Italy.

Vitina Grieco (V)

Laboratory of Clinical Research and Advanced Diagnostics, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, PZ, Italy.

Maddalena Maietti (M)

Unit of Clinical Pathology, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, PZ, Italy.

Antonio Traficante (A)

Unit of Clinical Pathology, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, PZ, Italy.

Teodora Statuto (T)

Laboratory of Clinical Research and Advanced Diagnostics, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, PZ, Italy.

Oreste Villani (O)

Hematology and Stem Cell Transplantation Unit, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, PZ, Italy.

Pellegrino Musto (P)

Hematology and Stem Cell Transplantation Unit, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, PZ, Italy.

Alessandro Sgambato (A)

Scientific Direction, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, PZ, Italy.

Luciana De Luca (L)

Laboratory of Clinical Research and Advanced Diagnostics, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, PZ, Italy.

Antonella Caivano (A)

Laboratory of Clinical Research and Advanced Diagnostics, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, PZ, Italy.

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