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

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.

Standardized procedure to measure the size distribution of extracellular vesicles together with other particles in biofluids with microfluidic resistive pulse sensing

“…This study did not assess the accuracy of MRPS or the effect of sample purification on the resulting PSD. Purified samples, in theory, could reduce the background noise during MRPS measurements, as purification techniques reduce the background noise in both similar and orthogonal particle size characterization techniques (TRPS, NTA, FCM, cryo-EM) [15,23,[34][35][36][37][38] and could presumably decrease the LoD. We now have a reliable and reproducible operating procedure for measuring the PSD and concentration of EVs together with other particles in biofluids, which is necessary before evaluating accuracy and precision.…”

Perspectives of Microscopy Methods for Morphology Characterisation of Extracellular Vesicles from Human Biofluids

“…EVs examined under buffer in liquid and in air conditions showed similar morphology in both media, spheroidal shape, around 30 nm high and 90 nm wide. Rikkert et al [145] investigated blood-derived EVs on a poly-Llysine coverslip by AFM in PBS environment with PFT mode using minimal imaging force. Their topography and mechanical properties were obtained from the force-indentation curves.…”

Multiorgan-on-a-Chip: A Systemic Approach To Model and Decipher Inter-Organ Communication

“…3D bioengineered constructs are therefore preferred. Of these, multicellular organoids and tumoroids [2,9,13,14,16,29,34] require appropriate environments for self-organization and differentiation [15] that can be provided by adequate matrices. Natural matrices are mostly employed, such as Matrigel [6,7], collagen [10, 27,64], hyaluronic acid [11,13,33], and gelatin [64].…”