bims-exocan 2023-06-18 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2023–06–18
six papers selected by
Muhammad Rizwan, COMSATS University

Clinical Impact of Exosomes in Colorectal Cancer Metastasis.
Exosomes in brain diseases: Pathogenesis and therapeutic targets.
Tumor-derived exosome ElNF1-AS1 affects the progression of gastric cancer by promoting M2 polarization of macrophages.
The Importance of Detecting, Quantifying, and Characterizing Exosomes as a New Diagnostic/Prognostic Approach for Tumor Patients.
MicroRNA analysis of Natural Killer cell-derived exosomes: the microRNA let-7b-5p is enriched in exosomes and participates in their anti-tumor effects against pancreatic cancer cells.
Exosomal microRNAs as novel diagnostic biomarkers in breast cancer: A systematic evaluation and meta-analysis.

ACS Appl Bio Mater. 2023 Jun 14.

Clinical Impact of Exosomes in Colorectal Cancer Metastasis.

Srestha Ghosh, Rajib Dhar, Gauresh Gurudas Shivji, Dwaipayan Dey, Arikketh Devi, Saurabh Kumar Jha, Manab Deb Adhikari, Sukhamoy Gorai.

  Cancer is a complex deadly disease that has caused a global health crisis in recent epochs. Colorectal cancer (CRC) is the third most common malignant gastrointestinal disease. It has led to high mortality due to early diagnostic failure. Extracellular vesicles (EVs) come with promising solutions for CRC. Exosomes (a subpopulation of EVs) play a vital role as signaling molecules in CRC tumor microenvironment. It is secreted from all active cells. Exosome-based molecular transport (DNA, RNA, proteins, lipids, etc.) transforms the recipient cell's nature. In CRC, tumor cell-derived exosomes (TEXs) regulate multiple events of CRC development and progression such as immunogenic suppression, angiogenesis, epithelial-mesenchymal transitions (EMT), physical changes in the extracellular matrix (ECM), and metastasis. Biofluid-circulated tumor-derived exosomes (TEXs) are a potential tool for CRC liquid biopsy. Exosome-based colorectal cancer detection creates a great impact in CRC biomarker research. The exosome-associated CRC theranostics approach is a state-of-the-art method. In this review, we address the CRC and exosomes complex associated with cancer development and progression, the impact of exosomes on CRC screening (diagnostic and prognostic biomarkers), and also highlight several exosomes with CRC clinical trials, as well as future directions of exosome-based CRC research. Hopefully, it will encourage several researchers to develop a potential exosome-based theranostic tool to fight CRC.

Keywords:  biomarkers; colon cancer; exosomes; metastasis; therapeutics

DOI:  https://doi.org/10.1021/acsabm.3c00199
MedComm (2020). 2023 Jun;4(3): e287

Exosomes in brain diseases: Pathogenesis and therapeutic targets.

Qingying Si, Linlin Wu, Deshui Pang, Pei Jiang.

  Exosomes are extracellular vesicles with diameters of about 100 nm that are naturally secreted by cells into body fluids. They are derived from endosomes and are wrapped in lipid membranes. Exosomes are involved in intracellular metabolism and intercellular communication. They contain nucleic acids, proteins, lipids, and metabolites from the cell microenvironment and cytoplasm. The contents of exosomes can reflect their cells' origin and allow the observation of tissue changes and cell states under disease conditions. Naturally derived exosomes have specific biomolecules that act as the "fingerprint" of the parent cells, and the contents changed under pathological conditions can be used as biomarkers for disease diagnosis. Exosomes have low immunogenicity, are small in size, and can cross the blood-brain barrier. These characteristics make exosomes unique as engineering carriers. They can incorporate therapeutic drugs and achieve targeted drug delivery. Exosomes as carriers for targeted disease therapy are still in their infancy, but exosome engineering provides a new perspective for cell-free disease therapy. This review discussed exosomes and their relationship with the occurrence and treatment of some neuropsychiatric diseases. In addition, future applications of exosomes in the diagnosis and treatment of neuropsychiatric disorders were evaluated in this review.

Keywords:  biomarker; diagnosis; exosomes; neuropsychiatric diseases; treatment

DOI:  https://doi.org/10.1002/mco2.287
Environ Toxicol. 2023 Jun 13.

Tumor-derived exosome ElNF1-AS1 affects the progression of gastric cancer by promoting M2 polarization of macrophages.

Bo Ma, Jun Wang, Paheredini Yusufu.

   BACKGROUND: This study attempted to investigate the role of exosome ELFN1-AS1 in gastric cancer (GC).
METHODS: The study used various techniques to determine the level of exosomal ELFN1-AS1 in GC tissue and cells, including quantitative real-time PCR. Pull-down assay and dual-luciferase reporter assay were employed to identify interactions between ELFN1-AS1 and miR-4644, as well as miR-4644 and PKM. Western blot was employed to explore the potential regulatory mechanism. Several in vitro assays were conducted in xenograft models to investigate the impacts of exosomal ELFN1-AS1 on GC development, metastasis and macrophage polarization.
RESULTS: ELFN1-AS1 was upregulated in GC tissue and cells, with high enrichment in GC-derived exosomes. Exosomal ELFN1-AS1 enhances the cell abilities and stemness of GC. ELFN1-AS1 targeted and regulated miR-4644, which triggered PKM expression. Exosomal ELFN1-AS1 modulated glycolysis via PKM in an HIF-1α dependent manner in GC, promoting M2 polarization and macrophage recruitment. Furthermore, exosomal ELFN1-AS1 enhanced GC cell growth, metastasis and M2 polarization in vivo.
CONCLUSIONS: The study suggests that ELFN1-AS1 could be a promising biomarker for the diagnosis and treatment of GC.

Keywords:  exosome; gastric cancer; glycolysis; lncRNA; macrophage polarization

DOI:  https://doi.org/10.1002/tox.23862
Cancers (Basel). 2023 May 23. pii: 2878. [Epub ahead of print]15(11):

The Importance of Detecting, Quantifying, and Characterizing Exosomes as a New Diagnostic/Prognostic Approach for Tumor Patients.

Mariantonia Logozzi, Nicola Salvatore Orefice, Rossella Di Raimo, Davide Mizzoni, Stefano Fais.

  Exosomes are extracellular vesicles (EVs) of nanometric size studied for their role in tumor pathogenesis and progression and as a new source of tumor biomarkers. The clinical studies have provided encouraging but probably unexpected results, including the exosome plasmatic levels' clinical relevance and well-known biomarkers' overexpression on the circulating EVs. The technical approach to obtaining EVs includes methods to physically purify EVs and characterize EVs, such as Nanosight Tracking Analysis (NTA), immunocapture-based ELISA, and nano-scale flow cytometry. Based on the above approaches, some clinical investigations have been performed on patients with different tumors, providing exciting and promising results. Here we emphasize data showing that exosome plasmatic levels are consistently higher in tumor patients than in controls and that plasmatic exosomes express well-known tumor markers (e.g., PSA and CEA), proteins with enzymatic activity, and nucleic acids. However, we also know that tumor microenvironment acidity is a key factor in influencing both the amount and the characteristics of the exosome released by tumor cells. In fact, acidity significantly increases exosome release by tumor cells, which correlates with the number of exosomes that circulate through the body of a tumor patient.

Keywords:  biomarkers; body fluids; exosomes; extracellular vesicles; methodology; plasma; tumors

DOI:  https://doi.org/10.3390/cancers15112878
Oncoimmunology. 2023 ;12(1): 2221081

MicroRNA analysis of Natural Killer cell-derived exosomes: the microRNA let-7b-5p is enriched in exosomes and participates in their anti-tumor effects against pancreatic cancer cells.

Anna Laura Di Pace, Andrea Pelosi, Piera Filomena Fiore, Nicola Tumino, Francesca Besi, Linda Quatrini, Silvia Santopolo, Paola Vacca, Lorenzo Moretta.

  Natural Killer (NK) cells are important components of the immune system in the defense against tumor growth and metastasis. They release exosomes containing proteins and nucleic acids, including microRNAs (miRNAs). NK-derived exosomes play a role in the anti-tumor NK cell function since they are able to recognize and kill cancer cells. However, the involvement of exosomal miRNAs in the function of NK exosomes is poorly understood. In this study, we explored the miRNA content of NK exosomes by microarray as compared to their cellular counterparts. The expression of selected miRNAs and lytic potential of NK exosomes against childhood B acute lymphoblastic leukemia cells after co-cultures with pancreatic cancer cells were also evaluated. We identified a small subset of miRNAs, including miR-16-5p, miR-342-3p, miR-24-3p, miR-92a-3p and let-7b-5p that is highly expressed in NK exosomes. Moreover, we provide evidence that NK exosomes efficiently increase let-7b-5p expression in pancreatic cancer cells and induce inhibition of cell proliferation by targeting the cell cycle regulator CDK6. Let-7b-5p transfer by NK exosomes could represent a novel mechanism by which NK cells counteract tumor growth. However, both cytolytic activity and miRNA content of NK exosomes were reduced upon co-culture with pancreatic cancer cells. Alteration in the miRNA cargo of NK exosomes, together with their reduced cytotoxic activity, could represent another strategy exerted by cancer to evade the immune response. Our study provides new information on the molecular mechanisms used by NK exosomes to exert anti-tumor-activity and offers new clues to integrate cancer treatments with NK exosomes.

Keywords:  Natural killer cells; exosomes; gene expression profiling; microRNA; tumor microenvironment

DOI:  https://doi.org/10.1080/2162402X.2023.2221081
Asian J Surg. 2023 Jun 08. pii: S1015-9584(23)00786-8. [Epub ahead of print]

Exosomal microRNAs as novel diagnostic biomarkers in breast cancer: A systematic evaluation and meta-analysis.

Fangcheng Hong, Ning Li, Zheming Feng, Yuxin Zheng, Chunyue Zhu, Fenghua Zhang.

  Circulating tumor-derived exosomal microRNAs (miRNAs) play a key role in the development of cancer. We aimed to assess the diagnostic value of circulating exosomal miRNAs in breast cancer (BC). A computer search was conducted for clinical studies on exosomal miRNA diagnosis of breast cancer published in Wanfang, CNKI, China Biology Medicine disc, VIP, Web of Science, Cochrane Library, PubMed, and Embase built up to August 16, 2022. True/false positive (TP/FP) and true/false negative (TN/FN) rates were extracted from each eligible study to obtain pooled sensitivities, specificities, positive/negative likelihood ratios (PLR/NLR), diagnostic odds ratio (DOR), and their 95% confidence intervals (95% CI). The meta-analysis included 7 articles including 348 Asian patients and 260 controls. All miRNAs were quantified using qRT-PCR assays. The sensitivity and specificity of the combination were 0.67 (95% CI = 0.64-0.71) and 0.81 (95% CI = 0.77-0.86), respectively. The combined DOR was 10.2 (95% CI = 6.00-16.74). The combined AUC(area under the subject operating characteristic curve) was 0.83 (0.91-0.96). In conclusion, exosomal-derived miRNA can be a good indicator to improve the diagnosis of breast cancer.

Keywords:  Breast cancer; Exosome; Liquid biopsy; Meta-Analysis; miRNAs

DOI:  https://doi.org/10.1016/j.asjsur.2023.05.115