The versatile role of exosomes in cancer progression: diagnostic and therapeutic implications

Sundararajan, Vignesh; Sarkar, Fazlul H.; Ramasamy, Thamil Selvee

doi:10.1007/s13402-018-0378-4

Cited by 58 publications

(40 citation statements)

References 237 publications

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“…As exosomes exist in various body fluids and exhibit specific molecular profiles depending on their cell of origin, exosomes have been considered the potential diagnostic biomarkers in cancer. Many methods, including flow cytometry, nanoparticle tracking analysis, enzyme‐linked immunosorbent assay combined with microfluidic platform, and electrochemical biosensors have been developed to achieve the quantification of exosomes (Table S3, Supporting Information) . Aptamers are short ssDNA or RNA molecules which can specifically bind to their targets.…”

Section: Introductionmentioning

confidence: 99%

A Sensitive Aptasensor Based on a Hemin/G‐Quadruplex‐Assisted Signal Amplification Strategy for Electrochemical Detection of Gastric Cancer Exosomes

Huang

Xia

et al. 2019

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Emerging evidence indicates that exosomes derived from gastric cancer cells enhance tumor migration and invasion through the modulation of the tumor microenvironment. However, it remains a major problem to detect cancer‐specific exosomes due to technical and biological challenges. Most of the methods reported could not achieve efficient detection of tumor‐derived exosomes in the background of normal exosomes. Herein, a label‐free electrochemical aptasensor is presented for specific detection of gastric cancer exosomes. This platform contains an anti‐CD63 antibody modified gold electrode and a gastric cancer exosome specific aptamer. The aptamer is linked to a primer sequence that is complementary to a G‐quadruplex circular template. The presence of target exosomes could trigger rolling circle amplification and produce multiple G‐quadruplex units. This horseradish peroxidase mimicking DNAzyme could catalyze the reduction of H2O2 and generate electrochemical signals. This aptasensor exhibits high selectivity and sensitivity toward gastric cancer exosomes with a detection limit of 9.54 × 102 mL−1 and a linear response range from 4.8 × 103 to 4.8 × 106 exosomes per milliliter. Therefore, this electrochemical aptasensor is expected to become a useful tool for the early diagnosis of gastric cancer.

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Section: Introductionmentioning

confidence: 99%

A Sensitive Aptasensor Based on a Hemin/G‐Quadruplex‐Assisted Signal Amplification Strategy for Electrochemical Detection of Gastric Cancer Exosomes

Huang

Xia

et al. 2019

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“…Exosomes are small lipid bilayer vesicles with a diameter of 30-120 nm secreted by various cell types and are taken up by neighboring or distant cells to develop mutually supportive positive feedback loops of cellular communication [13,14]. The main function of exosomes is to participate in cell-cell communication by transferring proteins, DNA, mRNAs, miRNAs and lncRNAs [11,15,16].…”

Section: Introductionmentioning

confidence: 99%

Exosomes derived from cancer stem cells of gemcitabine-resistant pancreatic cancer cells enhance drug resistance by delivering miR-210

et al. 2019

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Purpose Gemcitabine (GEM)-based chemotherapy is the first-line treatment for locally advanced pancreatic cancer. GEM resistance, however, remains a significant clinical challenge. Here, we investigated whether exosomes derived from GEMresistant pancreatic cancer stem cells (CSCs) mediate cell-cell communication between cells that are sensitive or resistant to GEM and, by doing so, regulate drug resistance. Methods GEM-sensitive BxPC-3-derived Bx S and PANC-1 pancreatic cancer cells were cultured with exosomes extracted from CSCs isolated from GEM-resistant BxPC-3-derived Bx R cells (Bx R -CSC). The effect of exosomes on drug resistance, cell cycle progression, apoptosis and miRNA expression was evaluated in Bx S and PANC-1 cells. Relevant miRNAs associated with GEM resistance were identified and the role of miR-210 in conferring drug resistance was examined in vitro and in vivo. Results Bx R -CSC-derived exosomes induced GEM resistance, inhibited GEM-induced cell cycle arrest, antagonized GEMinduced apoptosis, and promoted tube formation and cell migration in Bx S and PANC-1 cells. Elevated miR-210 expression levels were detected in Bx R -CSCs and Bx R -CSC-derived exosomes compared to those in Bx S -CSCs and Bx S -CSC-derived exosomes. In addition, increased expression levels of miR-210 were observed in Bx S and PANC-1 cells cultured with Bx R -CSCderived exosomes upon exposure to GEM in a dose-dependent manner. Also, a series of biological changes was observed in Bx S cells after transfection with miR-210 mimics, including activation of the mammalian target of rapamycin (mTOR) signaling pathway, and these changes were similar to those triggered by Bx R -CSC-derived exosomes. Conclusions Our findings suggest that exosomes derived from GEM-resistant pancreatic cancer stem cells mediate the horizontal transfer of drug-resistant traits to GEM-sensitive pancreatic cancer cells by delivering miR-210.

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“…Exosomal miRNAs may be derived from cancer cells themselves or from stromal cells like CAFs. To date, most studies have focused on exosomal miRNAs derived from cancer cells [19,20]. CAF-derived exosomal miRNAs are now receiving increasing attention, but no studies have yet been conducted to explore the aberrant expression pro les of exosomal miRNAs derived from CAFs in patients with SLSCC.…”

Section: Discussionmentioning

confidence: 99%

Aberrant expression profiles and bioinformatic analysis of CAF-derived exosomal miRNAs from three moderately differentiated supraglottic LSCC patients

Wang

Huang

et al. 2020

Preprint

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Background Aberrant expression of exosomal miRNAs has emerged as a research hotspot in cancer studies. However, no studies have been conducted on the dysregulation of exosomal miRNAs derived from cancer-associated fibroblasts (CAFs) in supraglottic laryngeal squamous cell carcinoma (SLSCC). Methods CAFs and paired normal fibroblasts (NFs) from SLSCC patients were cultured, and exosomes in the culture supernatants were collected and identified by transmission electron microscopy, nanoparticle tracking analysis and western blotting. Exosomal miRNA expression was compared in each pair of CAFs and NFs by next-generation sequencing. Four online bioinformatic algorithms predicted the potential target genes of aberrantly expressed miRNAs, while gene ontology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment and network analysis identified downstream target genes and their interactions. Results Three pairs of CAFs and NFs were successfully cultured and purified. CAF-derived exosomal miRNAs were mostly downregulated and included miR-656-3p, miR-337-5p, miR-29a-3p and miR-655-3p; however, some, including miR-184-3p, miR-92a-1-5p, miR-212-3p and miR-3135b, were upregulated. Bioinformatics analysis revealed involvement of these miRNAs in biological processes, cellular components and molecular functions. KEGG analysis revealed the top thirty pathways involvement in cancer initiation and progression and in cell cycle regulation. An interaction network showed miR-16-5p, miR-29a-3p, miR-34c-5p, miR-32-5p and miR-490-5p as the top five miRNAs and CCND1, CDKN1B, CDK6, PTEN and FOS as the top five target genes. Conclusions SLSCC patients showed aberrant expression of CAF-derived exosomal miRNAs. The target genes may jointly constitute a carcinogenic tumour microenvironment and may play decisive roles in the initiation and progression of SLSCC.

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The versatile role of exosomes in cancer progression: diagnostic and therapeutic implications

Abstract: This review highlights the important role of exosomes in cancer progression and its implications for (non-invasive) diagnostics and the development of novel therapeutic strategies, as well as its current and future applications in clinical trials.

Cited by 58 publications

References 237 publications

A Sensitive Aptasensor Based on a Hemin/G‐Quadruplex‐Assisted Signal Amplification Strategy for Electrochemical Detection of Gastric Cancer Exosomes

A Sensitive Aptasensor Based on a Hemin/G‐Quadruplex‐Assisted Signal Amplification Strategy for Electrochemical Detection of Gastric Cancer Exosomes

Exosomes derived from cancer stem cells of gemcitabine-resistant pancreatic cancer cells enhance drug resistance by delivering miR-210

Aberrant expression profiles and bioinformatic analysis of CAF-derived exosomal miRNAs from three moderately differentiated supraglottic LSCC patients

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