Cancer-ID: Toward Identification of Cancer by Tumor-Derived Extracellular Vesicles in Blood.

Linda Gerritdina Rikkert ,J Caro,Cornelis Otto ,Marca H M Wauben ,Wouter H Roos ,Guido Jenster ,Herman L Offerhaus ,Agustin Enciso‐Martinez ,Melissa C Piontek ,Leonie De Rond ,D Michiel Pegtel ,Richardus B.m Schasfoort ,Pepijn Beekman ,Gyllion Brian Loozen ,Edwin Van Der Pol ,F.a.w Coumans ,W Lee ,Rienk Nieuwland ,Han Zuilhof ,Ton G Van Leeuwen ,Séverine Le Gac ,Afroditi Nanou ,Leonardus Wendelinus Mathias Marie Terstappen

doi:10.3389/fonc.2020.00608

Abstract

Extracellular vesicles (EVs) have great potential as biomarkers since their composition and concentration in biofluids are disease state dependent and their cargo can contain disease-related information. Large tumor-derived EVs (tdEVs, >1 μm) in blood from cancer patients are associated with poor outcome, and changes in their number can be used to monitor therapy effectiveness. Whereas, small tumor-derived EVs (<1 μm) are likely to outnumber their larger counterparts, thereby offering better statistical significance, identification and quantification of small tdEVs are more challenging. In the blood of cancer patients, a subpopulation of EVs originate from tumor cells, but these EVs are outnumbered by non-EV particles and EVs from other origin. In the Dutch NWO Perspectief Cancer-ID program, we developed and evaluated detection and characterization techniques to distinguish EVs from non-EV particles and other EVs. Despite low signal amplitudes, we identified characteristics of these small tdEVs that may enable the enumeration of small tdEVs and extract relevant information. The insights obtained from Cancer-ID can help to explore the full potential of tdEVs in the clinic.

Highlights

Extracellular vesicles (EVs) are cell-derived particles with a phospholipid membrane
We show that transmission electron microscopy (TEM) images taken by operator selection, the current standard within the EV field, can be used to demonstrate the presence of EVs in a sample
We show that cells and EVs captured on functionalized substrates and in solution can be imaged by scanning electron microscopy (SEM)

Summary

Introduction

Extracellular vesicles (EVs) are cell-derived particles with a phospholipid membrane. *DL, detection limit; Thr, throughput in total number of (generic) particles per hour; T, expected time needed to find 1 tdEV () in a typical plasma sample.

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Results

Conclusion