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Role of Extracellular Vesicles in Cancer Progression

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: closed (30 April 2025) | Viewed by 4747

Special Issue Editor


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Guest Editor
Centro Nacional de Investigaciones Oncológicas, Madrid, Spain
Interests: exosomes; extracellular vesicles; metastasis; tumour immunity; liquid biopsy
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Special Issue Information

Dear Colleagues,

Extracellular vesicles (EVs) are a heterogenous group of membrane-bound vesicles secreted by cells across all living kingdoms. They take part in cell-to-cell communication, and the mechanisms, messages and efficiency of this exchange system are currently under extensive investigation as they are involved in multiple physiological, as well as pathological processes.

Remarkably, EV secretion appears to be augmented in tumor cells and has a relevant role in cancer progression, offering a highly effective way to modulate the tumor microenvironment, contributing to the formation of pre-metastatic and metastatic niches, and participating in the tumor–immune landscape cross-talk.

This Special Issue of Cancers seeks original articles and review manuscripts focused on (1) analyzing tumor EV cargo; (2) EV function in the tumor–microenvironment interplay; (3) their role as modulators of pre-metastatic and metastatic niches across various cancer types; (4) the influence of EVs on immune surveillance against tumors; and finally, (5) EV-based biomarkers and therapeutic development in cancer research.

Dr. Susana García-Silva
Guest Editor

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Keywords

  • extracellular vesicles
  • cancer progression
  • tumor microenvironment
  • tumor–immune landscape cross-talk pre-metastatic and metastatic niches
  • immune surveillance
  • EV-based biomarkers
  • EV-based therapeutic development

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Published Papers (3 papers)

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Research

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17 pages, 3072 KiB  
Article
NK3.3-Derived Extracellular Vesicles Penetrate and Selectively Kill Treatment-Resistant Tumor Cells
by Allyson McCune and Jacki Kornbluth
Cancers 2024, 16(1), 90; https://doi.org/10.3390/cancers16010090 - 23 Dec 2023
Cited by 4 | Viewed by 1943
Abstract
Cancer treatments often become ineffective due to the development of tumor resistance, leading to metastasis and relapse. Treatments may also fail because of their inability to access cells deep within the tumor tissue. When this occurs, new therapeutic agents are needed. We previously [...] Read more.
Cancer treatments often become ineffective due to the development of tumor resistance, leading to metastasis and relapse. Treatments may also fail because of their inability to access cells deep within the tumor tissue. When this occurs, new therapeutic agents are needed. We previously reported that NK3.3EVs, extracellular vesicles (EVs) derived from the normal human natural killer (NK) cell line, NK3.3, have strong cytotoxic activity against leukemia and breast cancer cell lines, without harming normal cells. Here, we used a three-dimensional (3D) MCF7 breast cancer mammosphere model to reproduce a more physiological environment that NK3.3EVs would encounter in vivo. NK3.3EVs penetrated MCF7 mammospheres, inducing death by apoptosis. We generated an imatinib-resistant K562 chronic myeloid leukemia (CML) cell line to investigate whether NK3.3EVs were able to kill tumor cells resistant to front-line chemotherapy. NK3.3EVs were even more cytotoxic to imatinib-resistant cells than parental cells, inducing apoptosis via caspase-3/-7 activation. The small population of cancer stem cells (CSCs) within tumors also contributes to therapeutic resistance. NK3.3EVs reduced the CSC-like CD34+/CD38− subpopulation in imatinib-resistant and parental K562 cultures and decreased CSC-associated expression of tumor-promoting genes. Our results provide strong evidence that NK3.3EVs may be a potential new immunotherapeutic agent for difficult-to-treat cancers. Full article
(This article belongs to the Special Issue Role of Extracellular Vesicles in Cancer Progression)
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Review

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25 pages, 1516 KiB  
Review
Bacterial Extracellular Vesicles in Oncology: Molecular Mechanisms and Future Clinical Applications
by Piyush Bhanu, Andrew K. Godwin, Shahid Umar and Diane E. Mahoney
Cancers 2025, 17(11), 1774; https://doi.org/10.3390/cancers17111774 - 26 May 2025
Viewed by 797
Abstract
Bacterial extracellular vesicles (BEVs) have emerged as pivotal mediators of host–microbe interactions, profoundly influencing cancer biology. These nanoscale vesicles, produced by both Gram-positive and Gram-negative bacteria, carry diverse biomolecular cargo such as proteins, lipids, nucleic acids, and metabolites. BEVs play dualistic roles in [...] Read more.
Bacterial extracellular vesicles (BEVs) have emerged as pivotal mediators of host–microbe interactions, profoundly influencing cancer biology. These nanoscale vesicles, produced by both Gram-positive and Gram-negative bacteria, carry diverse biomolecular cargo such as proteins, lipids, nucleic acids, and metabolites. BEVs play dualistic roles in tumor promotion and suppression by modulating the tumor microenvironment, immune responses, and genetic regulation. This review synthesizes the current understanding of BEVs in various cancers, including gastrointestinal, ovarian, breast, lung, brain, and renal malignancies. BEVs are highlighted for their potential as diagnostic biomarkers, prognostic indicators, and therapeutic agents, including their applications in immunotherapy and advanced engineering for precision medicine. Challenges such as heterogeneity, standardization, and clinical scalability are critically analyzed, with case examples providing actionable insights. Future directions emphasize interdisciplinary collaborations, emerging technologies, and the integration of BEV-based tools into clinical workflows. This review underscores the transformative potential of BEVs in advancing cancer diagnostics and therapeutics, paving the way for innovations in precision oncology. Full article
(This article belongs to the Special Issue Role of Extracellular Vesicles in Cancer Progression)
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19 pages, 2433 KiB  
Review
The Lymphatic Vascular System in Extracellular Vesicle-Mediated Tumor Progression
by Pragati Lodha, Alperen Acari, Jochen Rieck, Sarah Hofmann and Lothar C. Dieterich
Cancers 2024, 16(23), 4039; https://doi.org/10.3390/cancers16234039 - 2 Dec 2024
Cited by 1 | Viewed by 1579
Abstract
Tumor growth and progression require molecular interactions between malignant and host cells. In recent years, extracellular vesicles (EVs) emerged as an important pillar of such interactions, carrying molecular information from their donor cells to distant recipient cells. Thereby, the phenotype and function of [...] Read more.
Tumor growth and progression require molecular interactions between malignant and host cells. In recent years, extracellular vesicles (EVs) emerged as an important pillar of such interactions, carrying molecular information from their donor cells to distant recipient cells. Thereby, the phenotype and function of the recipient cells are altered, which may facilitate tumor immune escape and tumor metastasis to other organs through the formation of pre-metastatic niches. A prerequisite for these effects of tumor cell-derived EVs is an efficient transport system from the site of origin to the body periphery. Here, we highlight the role of the lymphatic vascular system in the distribution and progression-promoting functions of tumor cell-derived EVs. Importantly, the lymphatic vascular system is the primary drainage system for interstitial fluid and its soluble, particulate, and cellular contents, and therefore represents the principal route for regional (i.e., to tumor-draining lymph nodes) and systemic distribution of EVs derived from solid tumors. Furthermore, recent studies highlighted the tumor-draining lymph node as a crucial site where tumor-derived EVs exert their effects. A deeper mechanistic understanding of how EVs gain access to the lymphatic vasculature, how they interact with their recipient cells in tumor-draining lymph nodes and beyond, and how they induce phenotypic and functional maladaptation will be instrumental to identify new molecular targets and conceive innovative approaches for cancer therapy. Full article
(This article belongs to the Special Issue Role of Extracellular Vesicles in Cancer Progression)
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