The forces driving cancer extracellular vesicle secretion

Bebelman, Maarten P.; Janssen, Eline; Pegtel, D. Michiel; Crudden, Caitrin

doi:10.1016/j.neo.2020.11.011

Cited by 53 publications

(42 citation statements)

References 109 publications

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“…In addition, miR-1246 up-regulation in AP tissue samples did not reflect in AP plasma samples. Polyps tend to have lower ability of exosome production and thus of miR-1246 release into circulation, considering the adenomatous polyps as a precancerous condition [44,45]. Since our results were obtained from transcriptome and functional analyses in cancer tissues and cells lines, the oncogenic potential of miRNA-1246 should be further evaluated in a human organoid model derived from normal colon and adenomatous polyp tissues [46,47].…”

Section: Discussionmentioning

confidence: 97%

miRNome Profiling and Functional Analysis Reveal Involvement of hsa-miR-1246 in Colon Adenoma-Carcinoma Transition by Targeting AXIN2 and CFTR

Lukoševičius

Juzėnas

Šaltenienė

et al. 2022

IJMS

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Regulatory changes occurring early in colorectal cancer development remain poorly investigated. Since the majority of cases develop from polyps in the adenoma-carcinoma transition, a search of early molecular features, such as aberrations in miRNA expression occurring prior to cancer development, would enable identification of potentially causal, rather than consequential, candidates in the progression of polyp to cancer. In the current study, by employing small RNA-seq profiling of colon biopsy samples, we described differentially expressed miRNAs and their isoforms in the adenoma-carcinoma transition. Analysis of healthy-adenoma-carcinoma sequence in an independent validation group enabled us to identify early deregulated miRNAs including hsa-miR-1246 and hsa-miR-215-5p, the expressions of which are, respectively, gradually increasing and decreasing. Loss-of-function experiments revealed that inhibition of hsa-miR-1246 lead to reduced cell viability, colony formation, and migration rate, thereby indicating an oncogenic effect of this miRNA in vitro. Subsequent western blot and luciferase reporter assay provided evidence of hsa-miR-1246 being involved in the regulation of target AXIN2 and CFTR genes’ expression. To conclude, the present study revealed possible involvement of hsa-miR-1246 in early colorectal cancer development and regulation of tumor suppressors AXIN2 and CFTR.

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Section: Discussionmentioning

confidence: 97%

miRNome Profiling and Functional Analysis Reveal Involvement of hsa-miR-1246 in Colon Adenoma-Carcinoma Transition by Targeting AXIN2 and CFTR

Lukoševičius

Juzėnas

Šaltenienė

et al. 2022

IJMS

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“…To take full advantage of tEV, there is thus a need to better understand their kinetics during tumor development and therapy. Furthermore, there is a clear need to decipher why and how EV biogenesis ramps up in cancer cells, and what the specific avenues are for interventions (58). Here, we provide a much more granular insight into the composition and make-up of tEV in PDAC cell lines and in human plasma samples.…”

Section: Discussionmentioning

confidence: 97%

Single EV analysis (sEVA) of mutated proteins allows detection of stage 1 pancreatic cancer

Ferguson

Yang

Zelga

et al. 2021

Preprint

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Tumor cell derived extracellular vesicles (EV) are being explored as circulating biomarkers for cancer detection. Up to now however, clinical results have been mixed for a number of reasons including the predominant use of bulk measurements, the inability to differentiate tumor from host cell derived vesicles, the general absence of uniquely identifying biomarkers and the unknown frequency of stochastically distributed biomarkers into single circulating vesicles. We hypothesized that a single EV analysis (sEVA) technique could potentially improve diagnostic accuracy necessary to detect early cancers but the actual biomarker frequency and practical detection limits are currently unknown. Using pancreatic cancer, we carefully analyzed the composition of putative cancer markers in 11 established and new patient derived models. In parental PDAC cells positive for KRASmut and/or P53mut proteins only ~40% of EVs were also positive (range: 30-64%). This rate of positivity increased to 57% when additional PDAC biomarkers were considered (MUC1, EGFR, αFG-P4OH) in cell lines. In a blinded study involving 16 patients with surgically proven stage 1 PDAC, KRASmut and P53mut protein was detectable at much lower levels, generally in < 0.1% of vesicles. With the analytical capabilities of sEVA however, 15 of the 16 patients with stage 1 PDAC expressed low levels of biomarker positive EV. Using a modeling approach, we estimate that the current PDAC detection limit is at ~0.1 cm3 tumor volume, below clinical imaging capabilities. These findings establish the potential for single-EV analysis for early cancer detection.

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“…It should be emphasized, however, that studies have been reported showing that EVs from CSCs contribute significantly to tumor progression. Among the processes involved are tumor resistance, metastasis, angiogenesis, and maintenance of stemness and immune suppression [ 21 , 23 , 36 , 41 , 42 , 43 ]. The main role of EVs also includes their fusion with macrophages and other immune cells [ 30 , 31 ].…”

Section: Cscs and Their Evs Are Essential For Cancer Initiation And Its Processesmentioning

confidence: 99%

Cancer Stem Cells and Their Vesicles, Together with Other Stem and Non-Stem Cells, Govern Critical Cancer Processes: Perspectives for Medical Development

Meldolesi

2022

IJMS

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Stem cells, identified several decades ago, started to attract interest at the end of the nineties when families of mesenchymal stem cells (MSCs), concentrated in the stroma of most organs, were found to participate in the therapy of many diseases. In cancer, however, stem cells of high importance are specific to another family, the cancer stem cells (CSCs). This comprehensive review is focused on the role and the mechanisms of CSCs and of their specific extracellular vesicles (EVs), which are composed of both exosomes and ectosomes. Compared to non-stem (normal) cancer cells, CSCs exist in small populations that are preferentially distributed to the niches, such as minor specific tissue sites corresponding to the stroma of non-cancer tissues. At niches and marginal sites of other cancer masses, the tissue exhibits peculiar properties that are typical of the tumor microenvironment (TME) of cancers. The extracellular matrix (ECM) includes components different from non-cancer tissues. CSCs and their EVs, in addition to effects analogous to those of MSCs/EVs, participate in processes of key importance, specific to cancer: generation of distinct cell subtypes, proliferation, differentiation, progression, formation of metastases, immune and therapy resistance, cancer relapse. Many of these, and other, effects require CSC cooperation with surrounding cells, especially MSCs. Filtered non-cancer cells, especially macrophages and fibroblasts, contribute to collaborative cancer transition/integration processes. Therapy developments are mentioned as ongoing preclinical initiatives. The preliminary state of clinical medicine is presented in terms of both industrial development and future treatments. The latter will be administered to specific patients together with known drugs, with the aim of eradicating their tumor growth and metastases.

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The forces driving cancer extracellular vesicle secretion

Cited by 53 publications

References 109 publications

miRNome Profiling and Functional Analysis Reveal Involvement of hsa-miR-1246 in Colon Adenoma-Carcinoma Transition by Targeting AXIN2 and CFTR

miRNome Profiling and Functional Analysis Reveal Involvement of hsa-miR-1246 in Colon Adenoma-Carcinoma Transition by Targeting AXIN2 and CFTR

Single EV analysis (sEVA) of mutated proteins allows detection of stage 1 pancreatic cancer

Cancer Stem Cells and Their Vesicles, Together with Other Stem and Non-Stem Cells, Govern Critical Cancer Processes: Perspectives for Medical Development

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