Hematological Malignancy-Derived Small Extracellular Vesicles and Tumor Microenvironment: The Art of Turning Foes into Friends

Gargiulo, Ernesto; Paggetti, Jérôme; Moussay, Etienne

doi:10.3390/cells8050511

Cited by 27 publications

(29 citation statements)

References 236 publications

(302 reference statements)

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“…Researchers indicated that EVs play dual roles in regulating tumor growth depending on the source of EVs (Gargiulo et al, 2019;Han et al, 2019;Vermeer, 2019). For example, EVs derived from mature dendritic cells (DCs) contain phospholipids comprised of C22:6 docosahexaenoic acid (DHA), which enhance the antigen presenting ability of DCs and thus inhibit tumor cell proliferation (Pitt et al, 2016).…”

Section: Composition and Functions Of Evsmentioning

confidence: 99%

Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source

et al. 2020

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Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are nanosized membrane vesicles derived from most cell types. Carrying diverse biomolecules from their parent cells, EVs are important mediators of intercellular communication and thus play significant roles in physiological and pathological processes. Owing to their natural biogenesis process, EVs are generated with high biocompatibility, enhanced stability, and limited immunogenicity, which provide multiple advantages as drug delivery systems (DDSs) over traditional synthetic delivery vehicles. EVs have been reported to be used for the delivery of siRNAs, miRNAs, protein, small molecule drugs, nanoparticles, and CRISPR/Cas9 in the treatment of various diseases. As a natural drug delivery vectors, EVs can penetrate into the tissues and be bioengineered to enhance the targetability. Although EVs' characteristics make them ideal for drug delivery, EV-based drug delivery remains challenging, due to lack of standardized isolation and purification methods, limited drug loading efficiency, and insufficient clinical grade production. In this review, we summarized the current knowledge on the application of EVs as DDS from the perspective of different cell origin and weighted the advantages and bottlenecks of EV-based DDS. ARTICLE HISTORY

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Section: Composition and Functions Of Evsmentioning

confidence: 99%

Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source

et al. 2020

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“…Soluble molecules can be diluted by the large pool of circulating blood, while EV-associated molecules can be kept in a relatively concentrated microenvironment around the parental cells that release these EVs. Additionally, EVs can interact with cells/tissues across vast distances 28,29 . Therefore, we propose that EV-associated TOP may be important in GnRH processing and activity regulation in a systemic manner.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Thimet Oligopeptidase is Released with Extracellular Vesicles from Human Prostate Cancer Cells

Liu

Bruce

Wolfson

2020

Preprint

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Androgen signaling plays a central role in the development of prostate cancer. Androgen hormone synthesis is tightly governed by the hypothalamic-pituitary-gonadal (HPG) axis, including gonadotropin-releasing hormone (GnRH). Thimet oligopeptidase (TOP) is a biologically significant peptidase known to cleave GnRH and potentially regulate its activity.Thus, TOP can play an important role in the HPG axis through regulating the downstream production and release of gonadal steroid hormones, including androgens, which may further affect prostate cancer development. TOP is known to be secreted out to the extracellular space.Here, we report that extracellular TOP can be associated with extracellular vesicles (EVs).Western blot analysis of EVs isolated from PC3 or DU145 prostate cancer cells revealed that TOP protein is, indeed, carried by the EVs. Budding of EVs from stimulated PC3 prostate cancer cells can also be visualized by confocal microscopy. Significantly, the TOP enzyme carried by EVs is enzymatically active. The present study shows that EV-associated TOP is a novel form of this extracellular peptidase that may play a role in the disease progression of prostate cancer cells.

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“…Various studies in the literature described the capacity of cancer cell-derived sEVs not only to circumvent the canonical cellular defenses, but also to reshape the microenvironment of cells towards a malignant phenotype. By surrounding targeted tissues with pro-tumorigenic signals, cancer cell-derived sEVs can help in priming the pre-metastatic niche [67][68][69][70]. Only one miRNA with tumor suppressive functions (miR-122-3p) was found to be associated with sEVs [71].…”

Section: Discussionmentioning

confidence: 99%

Circulating miRNAs in Small Extracellular Vesicles Secreted by a Human Melanoma Xenograft in Mouse Brains

Guglielmi

Nardella

Musa

et al. 2020

Cancers

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The identification of liquid biomarkers remains a major challenge to improve the diagnosis of melanoma patients with brain metastases. Circulating miRNAs packaged into tumor-secreted small extracellular vesicles (sEVs) contribute to tumor progression. To investigate the release of tumor-secreted miRNAs by brain metastasis, we developed a xenograft model where human metastatic melanoma cells were injected intracranially in nude mice. The comprehensive profiles of both free miRNAs and those packaged in sEVs secreted by the melanoma cells in the plasma demonstrated that most (80%) of the sEV-associated miRNAs were also present in serum EVs from a cohort of metastatic melanomas, included in a publicly available dataset. Remarkably, among them, we found three miRNAs (miR-224-5p, miR-130a-3p and miR-21-5p) in sEVs showing a trend of upregulation during melanoma progression. Our model is proven to be valuable for identifying miRNAs in EVs that are unequivocally secreted by melanoma cells in the brain and could be associated to disease progression.

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Hematological Malignancy-Derived Small Extracellular Vesicles and Tumor Microenvironment: The Art of Turning Foes into Friends

Cited by 27 publications

References 236 publications

Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source

Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source

Extracellular Thimet Oligopeptidase is Released with Extracellular Vesicles from Human Prostate Cancer Cells

Circulating miRNAs in Small Extracellular Vesicles Secreted by a Human Melanoma Xenograft in Mouse Brains

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