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Guest Editor

Bioengineered 3D Microenvironments Group, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
Interests: leukaemia; cancer cell dormancy; drug resistance; measurable residual disease; liquid biopsy & cancer biomarkers; stress response; microenvironment-dependent drug resistance; organ-on-a-chip; bioengineered 3D microenvironments

Special Issue Information

Dear Colleagues,

Extracellular vesicles (EVs) are nanosized lipid membrane-enclosed vesicles that mediate intercellular signaling to coordinate the most complex physiological processes. Unsurprisingly, EV signaling networks are consistently transformed through the carcinogenesis process. Indeed, there is accumulating evidence strongly suggestive of the notion that cancers’ modus operandi for thriving are highly reliant on EV-mediated intercellular communication. Contrary to the once-prevalent dogma of “drug resistance by cancer genetics”, it has now become apparent that, for most cases, drug resistance seems to emerge from non-genetic changes at the tumor microenvironment. Importantly, these advantageous non-genetic features are conferred by EVs—occurring both in tumor and stromal cells—and enable cancer cells to adapt, survive drug exposure, relapse and metastasize later. Most interestingly, this EV dependency hallmark of cancer cells seems to hold true for many (if not all) human solid and liquid malignancies.

Thus, a timely and comprehensive understanding of how cancer-associated EVs enables tumor initiation, progression, drug resistance and relapse is instrumental for the development of innovative approaches that can have a transformative impact on both the early diagnosis and outcome of cancer treatment.

We invite you to contribute original research, technical notes, methods papers, and/or reviews to this Special Issue of “Surviving, Striving, Thriving: Exploring Extracellular Vesicles as Key Drivers of Cancer Cell Survival, Resistance and Relapse”. Papers that cover advances in the methods of cancer-associated EV isolation, analysis of the role of these vesicles in perpetuating cancer hallmarks, as well as their implementation both in basic research and the translational field of cancer biomarkers will be enthusiastically received by our readership. This Special Issue will aim to highlight significant advancements in understanding the intricate EV signaling networks that enable cancer cells to thrive, even under most adverse therapeutic pressure.

Dr. Hugo Ronaldo Freitas Caires
Guest Editor

Manuscript Submission Information

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Keywords

extracellular vesicles
cancer hallmarks
tumor microenvironment
drug resistance
biomarkers
solid & hematologic malignancies

Published Papers (2 papers)

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Research

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17 pages, 4356 KiB

Open AccessArticle

NGS Data Repurposing Allows Detection of tRNA Fragments as Gastric Cancer Biomarkers in Patient-Derived Extracellular Vesicles

and

Int. J. Mol. Sci. 2023, 24(10), 8961; https://doi.org/10.3390/ijms24108961 - 18 May 2023

Viewed by 1102

Abstract

Transfer RNA fragments (tRFs) have gene silencing effects similarly to miRNAs, can be sorted into extracellular vesicles (EVs) and are emerging as potential circulating biomarkers for cancer diagnoses. We aimed at analyzing the expression of tRFs in gastric cancer (GC) and understanding their potential as biomarkers. We explored miRNA datasets from gastric tumors and normal adjacent tissues (NATs) from TCGA repository, as well as proprietary 3D-cultured GC cell lines and corresponding EVs, in order to identify differentially represented tRFs using MINTmap and R/Bioconductor packages. Selected tRFs were validated in patient-derived EVs. We found 613 Differentially Expressed (DE)-tRFs in the TCGA dataset, of which 19 were concomitantly upregulated in TCGA gastric tumors and present in 3D cells and EVs, but barely expressed in NATs. Moreover, 20 tRFs were expressed in 3D cells and EVs and downregulated in TCGA gastric tumors. Of these 39 DE-tRFs, 9 tRFs were also detected in patient-derived EVs. Interestingly, the targets of these 9 tRFs affect neutrophil activation and degranulation, cadherin binding, focal adhesion and the cell–substrate junction, highlighting these pathways as major targets of EV-mediated crosstalk with the tumor microenvironment. Furthermore, as they are present in four distinct GC datasets and can be detected even in low quality patient-derived EV samples, they hold promise as GC biomarkers. By repurposing already available NGS data, we could identify and cross-validate a set of tRFs holding potential as GC diagnosis biomarkers. Full article

(This article belongs to the Special Issue Surviving, Striving, Thriving: Exploring Extracellular Vesicles as Key Drivers of Cancer Cell Survival, Resistance and Relapse)

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Review

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21 pages, 1142 KiB

Open AccessReview

Influence of Extracellular Vesicles on Lung Stromal Cells during Breast Cancer Metastasis

Urvi Patel

David Susman

and

Alison L. Allan

Int. J. Mol. Sci. 2023, 24(14), 11801; https://doi.org/10.3390/ijms241411801 - 22 Jul 2023

Viewed by 948

Abstract

Breast cancer is a prominent cause of cancer diagnosis and death in women globally, with over 90% of deaths being attributed to complications that arise from metastasis. One of the common locations for breast cancer metastasis is the lung, which is associated with significant morbidity and mortality. Curative treatments for metastatic breast cancer patients are not available and the molecular mechanisms that underlie lung metastasis are not fully understood. In order to better treat these patients, identifying events that occur both prior to and during metastatic spread to the lung is essential. Several studies have demonstrated that breast cancer-derived extracellular vesicles secreted from the primary breast tumor play a key role in establishing the lung pre-metastatic niche to support colonization of metastatic tumor cells. In this review, we summarize recent work supporting the influence of extracellular vesicles on stromal components of the lung to construct the pre-metastatic niche and support metastasis. Furthermore, we discuss the potential clinical applications of utilizing extracellular vesicles for diagnosis and treatment. Together, this review highlights the dynamic nature of extracellular vesicles, their roles in breast cancer metastasis to the lung, and their value as potential biomarkers and therapeutics for cancer prevention. Full article

(This article belongs to the Special Issue Surviving, Striving, Thriving: Exploring Extracellular Vesicles as Key Drivers of Cancer Cell Survival, Resistance and Relapse)

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