scholarly journals Correction: Yun et al. Prion Protein of Extracellular Vesicle Regulates the Progression of Colorectal Cancer. Cancers 2021, 13, 2144

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3560
Author(s):  
Chul-Won Yun ◽  
Jun-Hee Lee ◽  
Gyeongyun Go ◽  
Juhee Jeon ◽  
Sungtae Yoon ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prion Protein ◽  
Extracellular Vesicle

The authors wish to make the following corrections to this paper [...]

scholarly journals Prion Protein of Extracellular Vesicle Regulates the Progression of Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2144
Author(s):  
Chul-Won Yun ◽  
Jun-Hee Lee ◽  
Gyeongyun Go ◽  
Juhee Jeon ◽  
Sungtae Yoon ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prion Protein ◽  
Cell Communication ◽  
Xenograft Model ◽  
Endothelial Permeability ◽  
Extracellular Vesicle ◽  
Cellular Prion Protein ◽  
Murine Xenograft Model ◽  
Key Factor ◽  
Effective Therapeutic Strategy

Colorectal cancer (CRC) is one of the leading causes of cancer-related death due to its aggressive metastasis in later stages. Although there is a growing interest in the tumorigenic role of cellular prion protein (PrPC) in the process of metastasis, the precise mechanism behind the cellular communication involving prion proteins remains poorly understood. This study found that hypoxic tumor microenvironment increased the PrPC-expressing exosomes from CRC, and these exosomes regulate the CRC cell behavior and tumor progression depending on the expression of PrPC. Hypoxic exosomes from CRC cells promoted sphere formation, the expression of tumor-inducing genes, migration, invasion, and tumor growth. Furthermore, these exosomes increased endothelial permeability, migration, invasion, and angiogenic cytokine secretion. These effects were associated with PrPC expression. Application of anti-PrPC antibody with 5-fluorouracil significantly suppressed the CRC progression in a murine xenograft model. Taken together, these findings indicate that PrP-expressing exosomes secreted by hypoxic CRC cells are a key factor in the tumorigenic CRC-to-CRC and CRC-to-endothelial cell communication. Significance: These findings suggest that inhibiting PrPC in hypoxic exosomes during chemotherapy may be an effective therapeutic strategy in colorectal cancer.

scholarly journals Small EVs-Associated DNA as Complementary Biomarker to Circulating Tumor DNA in Plasma of Metastatic Colorectal Cancer Patients

2021 ◽  
Vol 14 (2) ◽  
pp. 128
Author(s):  
Silvia Galbiati ◽  
Francesco Damin ◽  
Dario Brambilla ◽  
Lucia Ferraro ◽  
Nadia Soriani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Digital Pcr ◽  
Extracellular Vesicle ◽  
Circulating Tumor Dna ◽  
Mutation Status ◽  
Promising Practice ◽  
Colorectal Cancer Patients ◽  
Tumor Dna

It is widely accepted that assessing circular tumor DNA (ctDNA) in the plasma of cancer patients is a promising practice to evaluate somatic mutations from solid tumors noninvasively. Recently, it was reported that isolation of extracellular vesicles improves the detection of mutant DNA from plasma in metastatic patients; however, no consensus on the presence of dsDNA in exosomes has been reached yet. We analyzed small extracellular vesicle (sEV)-associated DNA of eleven metastatic colorectal cancer (mCRC) patients and compared the results obtained by microarray and droplet digital PCR (ddPCR) to those reported on the ctDNA fraction. We detected the same mutations found in tissue biopsies and ctDNA in all samples but, unexpectedly, in one sample, we found a KRAS mutation that was not identified either in ctDNA or tissue biopsy. Furthermore, to assess the exact location of sEV-associated DNA (outside or inside the vesicle), we treated with DNase I sEVs isolated with three different methodologies. We found that the DNA inside the vesicles is only a small fraction of that surrounding the vesicles. Its amount seems to correlate with the total amount of circulating tumor DNA. The results obtained in our experimental setting suggest that integrating ctDNA and sEV-associated DNA in mCRC patient management could provide a complete real-time assessment of the cancer mutation status.

scholarly journals IFITM1 expression determines extracellular vesicle uptake in colorectal cancer

2021 ◽  
Author(s):  
Andrea Kelemen ◽  
Idan Carmi ◽  
Ádám Oszvald ◽  
Péter Lőrincz ◽  
Gábor Petővári ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Transmembrane Protein ◽  
Extracellular Vesicle ◽  
Cellular Heterogeneity ◽  
Functional Difference ◽  
Proliferating Cells ◽  
Antiviral Responses ◽  
The Difference ◽  
Functional Relevance ◽  
Therapeutic Tools

AbstractThe majority of colorectal cancer (CRC) patients carry mutations in the APC gene, which lead to the unregulated activation of the Wnt pathway. Extracellular vesicles (EV) are considered potential therapeutic tools. Although CRC is a genetically heterogeneous disease, the significance of the intra-tumor heterogeneity in EV uptake of CRC cells is not yet known. By using mouse and patient-derived organoids, the currently available best model of capturing cellular heterogeneity, we found that Apc mutation induced the expression of interferon-induced transmembrane protein 1 (Ifitm1), a membrane protein that plays a major role in cellular antiviral responses. Importantly, organoids derived from IFITM1high CRC cells contained more proliferating cells and they had a markedly reduced uptake of fibroblast EVs as compared to IFITM1low/− cells. In contrast, there was no difference in the intensity of EV release between CRC subpopulations with high and low IFITM1 levels. Importantly, the difference in cell proliferation between these two subpopulations disappeared in the presence of fibroblast-derived EVs, proving the functional relevance of the enhanced EV uptake by IFITM1low CRC cells. Furthermore, inactivating IFITM1 resulted in an enhanced EV uptake, highlighting the importance of this molecule in establishing the cellular difference for EV effects. Collectively, we identified CRC cells with functional difference in their EV uptake ability that must be taken into consideration when using EVs as therapeutic tools for targeting cancer cells.

scholarly journals Extracellular vesicle-miRNAs as liquid biopsy biomarkers for disease identification and prognosis in metastatic colorectal cancer patients

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Diego de Miguel Pérez ◽  
Alba Rodriguez Martínez ◽  
Alba Ortigosa Palomo ◽  
Mayte Delgado Ureña ◽  
Jose Luis Garcia Puche ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Extracellular Vesicle ◽  
Disease Identification ◽  
Colorectal Cancer Patients

scholarly journals Extracellular vesicle release from intestinal organoids is modulated by Apc mutation and other colorectal cancer progression factors

2019 ◽  
Vol 76 (12) ◽  
pp. 2463-2476 ◽  
Author(s):  
Zsuzsanna Szvicsek ◽  
Ádám Oszvald ◽  
Lili Szabó ◽  
Gyöngyvér Orsolya Sándor ◽  
Andrea Kelemen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Extracellular Vesicle ◽  
Vesicle Release ◽  
Intestinal Organoids ◽  
Colorectal Cancer Progression ◽  
Apc Mutation

scholarly journals The Impact of Diet on the Involvement of Non-Coding RNAs, Extracellular Vesicles, and Gut Microbiome-Virome in Colorectal Cancer Initiation and Progression

2020 ◽  
Vol 10 ◽  
Author(s):  
Bene A. Ekine-Afolabi ◽  
Anoka A. Njan ◽  
Solomon O. Rotimi ◽  
Anu R. I. ◽  
Attia M. Elbehi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Dna Methyltransferase ◽  
Molecular Mechanisms ◽  
Cell Communication ◽  
Extracellular Vesicle ◽  
Dietary Factors ◽  
Tumor Onset ◽  
Non Coding Rnas ◽  
The Impact

Cancer is the major cause of morbidity and mortality in the world today. The third most common cancer and which is most diet related is colorectal cancer (CRC). Although there is complexity and limited understanding in the link between diet and CRC, the advancement in research methods have demonstrated the involvement of non-coding RNAs (ncRNAs) as key regulators of gene expression. MicroRNAs (miRNAs) which are a class of ncRNAs are key players in cancer related pathways in the context of dietary modulation. The involvement of ncRNA in cancer progression has recently been clarified throughout the last decade. ncRNAs are involved in biological processes relating to tumor onset and progression. The advances in research have given insights into cell to cell communication, by highlighting the pivotal involvement of extracellular vesicle (EV) associated-ncRNAs in tumorigenesis. The abundance and stability of EV associated ncRNAs act as a new diagnostic and therapeutic target for cancer. The understanding of the deranging of these molecules in cancer can give access to modulating the expression of the ncRNAs, thereby influencing the cancer phenotype. Food derived exosomes/vesicles (FDE) are gaining interest in the implication of exosomes in cell-cell communication with little or no understanding to date on the role FDE plays. There are resident microbiota in the colon; to which the imbalance in the normal intestinal occurrence leads to chronic inflammation and the production of carcinogenic metabolites that lead to neoplasm. Limited studies have shown the implication of various types of microbiome in CRC incidence, without particular emphasis on fungi and protozoa. This review discusses important dietary factors in relation to the expression of EV-associated ncRNAs in CRC, the impact of diet on the colon ecosystem with particular emphasis on molecular mechanisms of interactions in the ecosystem, the influence of homeostasis regulators such as glutathione, and its conjugating enzyme-glutathione S-transferase (GST) polymorphism on intestinal ecosystem, oxidative stress response, and its relationship to DNA adduct fighting enzyme-0-6-methylguanine-DNA methyltransferase. The understanding of the molecular mechanisms and interaction in the intestinal ecosystem will inform on the diagnostic, preventive and prognosis as well as treatment of CRC.

scholarly journals The cellular prion protein controls the mesenchymal-like molecular subtype and predicts disease outcome in colorectal cancer

EBioMedicine ◽  
2019 ◽  
Vol 46 ◽  
pp. 94-104 ◽  
Author(s):  
Delphine Le Corre ◽  
Alexandre Ghazi ◽  
Ralyath Balogoun ◽  
Camilla Pilati ◽  
Thomas Aparicio ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prion Protein ◽  
Molecular Subtype ◽  
Cellular Prion Protein ◽  
Disease Outcome

scholarly journals Extracellular Vesicle-derived circular RNAs confers chemoresistance in Colorectal cancer

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kha Wai Hon ◽  
Nurul Syakima Ab-Mutalib ◽  
Nik Muhd Aslan Abdullah ◽  
Rahman Jamal ◽  
Nadiah Abu
Keyword(s):  
Colorectal Cancer ◽  
Extracellular Vesicle ◽  
Circular Rnas ◽  
Serum Samples ◽  
Transmission Electron ◽  
Potential Biomarker ◽  
Drug Sensitivity Assay ◽  
Drug Induction ◽  
Early Biomarker ◽  
Sirna Knockdown

Abstract Chemo-resistance is associated with poor prognosis in colorectal cancer (CRC), with the absence of early biomarker. Exosomes are microvesicles released by body cells for intercellular communication. Circular RNAs (circRNAs) are non-coding RNAs with covalently closed loops and enriched in exosomes. Crosstalk between circRNAs in exosomes and chemo-resistance in CRC remains unknown. This research aims to identify exosomal circRNAs associated with FOLFOX-resistance in CRC. FOLFOX-resistant HCT116 CRC cells (HCT116-R) were generated from parental HCT116 cells (HCT116-P) using periodic drug induction. Exosomes were characterized using transmission electron microscopy (TEM), Zetasizer and Western blot. Our exosomes were translucent cup-shaped structures under TEM with differential expression of TSG101, CD9, and CD63. We performed circRNAs microarray using exosomal RNAs from HCT116-R and HCT116-P cells. We validated our microarray data using serum samples. We performed drug sensitivity assay and cell cycle analysis to characterize selected circRNA after siRNA-knockdown. Using fold change >2 and p < 0.05, we identified 105 significantly upregulated and 34 downregulated circRNAs in HCT116-R exosomes. Knockdown of circ_0000338 improved the chemo-resistance of CRC cells. We have proposed that circ_0000338 may have dual regulatory roles in chemo-resistant CRC. Exosomal circ_0000338 could be a potential biomarker for further validation in CRC.

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