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Microvesicles in Cancer: Small Size, Large Potential.

ABSTRACT: Extracellular vesicles (EV) are secreted by all cell types in a tumor and its microenvironment (TME), playing an essential role in intercellular communication and the establishment of a TME favorable for tumor invasion and metastasis. They encompass a variety of vesicle populations, among them the well-known endosomal-derived small exosomes (Exo), but also larger vesicles (diameter > 100 nm) that are shed directly from the plasma membrane, the so-called microvesicles (MV). Increasing evidence suggests that MV, although biologically different, share the tumor-promoting features of Exo in the TME. Due to their larger size, they can be readily harvested from patients' blood and characterized by routine methods such as conventional flow cytometry, exploiting the plethora of molecules expressed on their surface. In this review, we summarize the current knowledge about the biology and the composition of MV, as well as their role within the TME. We highlight not only the challenges and potential of MV as novel biomarkers for cancer, but also discuss their possible use for therapeutic intervention.

SUBMITTER: Menck K

PROVIDER: S-EPMC7432491 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Microvesicles in Cancer: Small Size, Large Potential.

Menck Kerstin K Sivaloganathan Suganja S Bleckmann Annalen A Binder Claudia C

International journal of molecular sciences 20200728 15

Extracellular vesicles (EV) are secreted by all cell types in a tumor and its microenvironment (TME), playing an essential role in intercellular communication and the establishment of a TME favorable for tumor invasion and metastasis. They encompass a variety of vesicle populations, among them the well-known endosomal-derived small exosomes (Exo), but also larger vesicles (diameter > 100 nm) that are shed directly from the plasma membrane, the so-called microvesicles (MV). Increasing evidence su ...[more]

PMID: 32731639

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Project description:BackgroundEarly detection of small cell lung cancer (SCLC) crucially demands highly reliable markers. Growing evidence suggests that extracellular vesicles carry tumor cell-specific cargo suitable as protein markers in cancer. Quantitative proteomic profiling of circulating microvesicles and exosomes can be a high-throughput platform for discovery of novel molecular insights and putative markers. Hence, this study aimed to investigate proteome dynamics of plasma-derived microvesicles and exosomes in newly diagnosed SCLC patients to improve early detection.MethodsPlasma-derived microvesicles and exosomes from 24 healthy controls and 24 SCLC patients were isolated from plasma by either high-speed- or ultracentrifugation. Proteins derived from these extracellular vesicles were quantified using label-free mass spectrometry and statistical analysis was carried out aiming at identifying significantly altered protein expressions between SCLC patients and healthy controls. Furthermore, significantly expressed proteins were subjected to functional enrichment analysis to identify biological pathways implicated in SCLC pathogenesis.ResultsBased on fold change (FC) ≥ 2 or ≤ 0.5 and AUC ≥ 0.70 (p < 0.05), we identified 10 common and 16 and 17 unique proteins for microvesicles and exosomes, respectively. Among these proteins, we found dysregulation of coagulation factor XIII A (Log2 FC = - 1.1, p = 0.0003, AUC = 0.82, 95% CI: 0.69-0.96) and complement factor H-related protein 4 (Log2 FC = 1.2, p = 0.0005, AUC = 0.82, 95% CI; 0.67-0.97) in SCLC patients compared to healthy individuals. Our data may indicate a novel tumor-suppressing role of blood coagulation and involvement of complement activation in SCLC pathogenesis.ConclusionsIn comparing SCLC patients and healthy individuals, several differentially expressed proteins were identified. This is the first study showing that circulating extracellular vesicles may encompass specific proteins with potential diagnostic attributes for SCLC, thereby opening new opportunities as novel non-invasive markers.

Project description:Biomarkers are of tremendous importance for the prediction, diagnosis, and observation of the therapeutic success of common complex multifactorial metabolic diseases, such as type II diabetes and obesity. However, the predictive power of the traditional biomarkers used (eg, plasma metabolites and cytokines, body parameters) is apparently not sufficient for reliable monitoring of stage-dependent pathogenesis starting with the healthy state via its initiation and development to the established disease and further progression to late clinical outcomes. Moreover, the elucidation of putative considerable differences in the underlying pathogenetic pathways (eg, related to cellular/tissue origin, epigenetic and environmental effects) within the patient population and, consequently, the differentiation between individual options for disease prevention and therapy - hallmarks of personalized medicine - plays only a minor role in the traditional biomarker concept of metabolic diseases. In contrast, multidimensional and interdependent patterns of genetic, epigenetic, and phenotypic markers presumably will add a novel quality to predictive values, provided they can be followed routinely along the complete individual disease pathway with sufficient precision. These requirements may be fulfilled by small membrane vesicles, which are so-called exosomes and microvesicles (EMVs) that are released via two distinct molecular mechanisms from a wide variety of tissue and blood cells into the circulation in response to normal and stress/pathogenic conditions and are equipped with a multitude of transmembrane, soluble and glycosylphosphatidylinositol-anchored proteins, mRNAs, and microRNAs. Based on the currently available data, EMVs seem to reflect the diverse functional and dysfunctional states of the releasing cells and tissues along the complete individual pathogenetic pathways underlying metabolic diseases. A critical step in further validation of EMVs as biomarkers will rely on the identification of unequivocal correlations between critical disease states and specific EMV signatures, which in future may be determined in rapid and convenient fashion using nanoparticle-driven biosensors.

Dataset Information

Microvesicles in Cancer: Small Size, Large Potential.

Publications

Microvesicles in Cancer: Small Size, Large Potential.

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