bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2023–09–17
ten papers selected by
Muhammad Rizwan, COMSATS University
  1. Exosome-mediated metabolic reprogramming: Implications in esophageal carcinoma progression and tumor microenvironment remodeling.
  2. Emerging functions and applications of exosomes in oral squamous cell carcinoma.
  3. Engineered Exosomes as Theranostic Platforms for Cancer Treatment.
  4. Key role of exosomes derived from M2 macrophages in maintaining cancer cell stemness (Review).
  5. Breakthrough in large-scale production of iPSCs-derived exosomes to promote clinical applications.
  6. Colorectal cancer cell-secreted exosomal miRNA N-72 promotes tumor angiogenesis by targeting CLDN18.
  7. Identification of the SNARE complex that mediates the fusion of multivesicular bodies with the plasma membrane in exosome secretion.
  8. Extracellular vesicles as a potential source of tumor-derived DNA in advanced pancreatic cancer.
  9. MicroRNA Profiling in Circulating Exosomes in Oral Squamous Cell Carcinoma: A Systematic Review.
  10. Identification of exosomal microRNA panel as diagnostic and prognostic biomarker for small cell lung cancer.
  1. Cytokine Growth Factor Rev. 2023 Aug 30. pii: S1359-6101(23)00056-4. [Epub ahead of print]
    Exosome-mediated metabolic reprogramming: Implications in esophageal carcinoma progression and tumor microenvironment remodeling.
    Yong Xi, Yaxing Shen, Lijie Chen, Lijie Tan, Weiyu Shen, Xing Niu.
      Esophageal carcinoma is among the most fatal malignancies with increasing incidence globally. Tumor onset and progression can be driven by metabolic reprogramming, especially during esophageal carcinoma development. Exosomes, a subset of extracellular vesicles, display an average size of ∼100 nanometers, containing multifarious components (nucleic acids, proteins, lipids, etc.). An increasing number of studies have shown that exosomes are capable of transferring molecules with biological functions into recipient cells, which play crucial roles in esophageal carcinoma progression and tumor microenvironment that is a highly heterogeneous ecosystem through rewriting the metabolic processes in tumor cells and environmental stromal cells. The review introduces the reprogramming of glucose, lipid, amino acid, mitochondrial metabolism in esophageal carcinoma, and summarize current pharmaceutical agents targeting such aberrant metabolism rewiring. We also comprehensively overview the biogenesis and release of exosomes, and recent advances of exosomal cargoes and functions in esophageal carcinoma and their promising clinical application. Moreover, we discuss how exosomes trigger tumor growth, metastasis, drug resistance, and immunosuppression as well as tumor microenvironment remodeling through focusing on their capacity to transfer materials between cells or between cells and tissues and modulate metabolic reprogramming, thus providing a theoretical reference for the design potential pharmaceutical agents targeting these mechanisms. Altogether, our review attempts to fully understand the significance of exosome-based metabolic rewriting in esophageal carcinoma progression and remodeling of the tumor microenvironment, bringing novel insights into the prevention and treatment of esophageal carcinoma in the future.
    Keywords:  Esophageal carcinoma; Exosome; Lipid metabolism; Metabolic reprogramming; Tumor microenvironment; Tumor progression
    DOI:  https://doi.org/10.1016/j.cytogfr.2023.08.010
  2. J Oral Pathol Med. 2023 Sep 13.
    Emerging functions and applications of exosomes in oral squamous cell carcinoma.
    Yingchun Qie, Xia Sun, Yongqiang Yang, Tao Yan.
      Oral squamous cell carcinoma is the most common phenotype in pathology, which accounts for 80% of all oral cancers. The therapeutic methods of oral squamous cell carcinoma include surgical excision, chemotherapy, and radiotherapy. Whereas, the high recurrence rate and poor prognosis lead to a 5-year survival rate less than 50%. In order to explore more therapeutic strategies of oral squamous cell carcinoma, the relevant risk factors, mechanisms, and diagnostics are widely detected. The various exosome-mediated biological effects on the development of oral squamous cell carcinoma have drawn lots of attention. Exosomes, a kind of extracellular vesicles secreted from host cells and transferred to other cells, show great potential in the regulations of tumorigenesis, progression, and metastasis on oral squamous cell carcinoma. Moreover, some studies reported that the exosomes could interact with tumor microenvironment and be applied to diagnosis or therapy of oral squamous cell carcinoma. In this work, we will summarize the frontier studies of exosomes in the tumor growth, tumor-associated angiogenesis, invasion, and metastasis of oral squamous cell carcinoma, and then probe the current biological functions and applications of exosomes and exosome-derived materials for the therapeutic strategies of oral squamous cell carcinoma, which would help us to update the understanding of exosomes in oral squamous cell carcinoma.
    Keywords:  exosomes; extracellular vesicles; oral cancer; oral squamous cell carcinoma; tumorigenesis
    DOI:  https://doi.org/10.1111/jop.13479
  3. ACS Biomater Sci Eng. 2023 Sep 11.
    Engineered Exosomes as Theranostic Platforms for Cancer Treatment.
    Xu Yang, Xiangyu Xie, Songbin Liu, Wei Ma, Zhi Zheng, Hua Wei, Cui-Yun Yu.
      Tremendous progress in nanotechnology and nanomedicine has made a significant positive effect on cancer treatment by integrating multicomponents into a single multifunctional nanosized delivery system for combinatorial therapies. Although numerous nanocarriers developed so far have achieved excellent therapeutic performance in mouse models via elegant integration of chemotherapy, photothermal therapy, photodynamic therapy, sonodynamic therapy, and immunotherapy, their synthetic origin may still cause systemic toxicity, immunogenicity, and preferential detection or elimination by the immune system. Exosomes, endogenous nanosized particles secreted by multiple biological cells, could be absorbed by recipient cells to facilitate intercellular communication and content delivery. Therefore, exosomes have emerged as novel cargo delivery tools and attracted considerable attention for cancer diagnosis and treatment due to their innate stability, biological compatibility, and biomembrane penetration capacity. Exosome-related properties and functions have been well-documented; however, there are few reviews, to our knowledge, with a focus on the combination of exosomes and nanotechnology for the development of exosome-based theranostic platforms. To make a timely review on this hot subject of research, we summarize the basic information, isolation and functionalization methodologies, diagnostic and therapeutic potential of exosomes in various cancers with an emphasis on the description of exosome-related nanomedicine for cancer theranostics. The existing appealing challenges and outlook in exosome clinical translation are finally introduced. Advanced biotechnology and nanotechnology will definitely not only promote the integration of intrinsic advantages of natural nanosized exosomes with traditional synthetic nanomaterials for modulated precise cancer treatment but also contribute to the clinical translations of exosome-based nanomedicine as theranostic nanoplatforms.
    Keywords:  cancer; diagnosis; exosome; nanomedicine; therapy
    DOI:  https://doi.org/10.1021/acsbiomaterials.3c00745
  4. Int J Oncol. 2023 Nov;pii: 126. [Epub ahead of print]63(5):
    Key role of exosomes derived from M2 macrophages in maintaining cancer cell stemness (Review).
    Weiqiong Zhang, Ruiping Zhou, Xin Liu, Lin You, Chang Chen, Xiaoling Ye, Jie Liu, Youde Liang.
      Cancer stem cells (CSCs) constitute a specific subset of cells found within tumors that are responsible for initiating, advancing and resisting traditional cancer treatments. M2 macrophages, also known as alternatively activated macrophages, contribute to the development and progression of cancer through their involvement in promoting angiogenesis, suppressing the immune system, supporting tumor growth and facilitating metastasis. Exosomes, tiny vesicles released by cells, play a crucial role in intercellular communications and have been shown to be associated with cancer development and progression by influencing the immune response; thus, they may serve as markers for diagnosis and prognosis. Currently, investigating the impact of exosomes derived from M2 macrophages on the maintenance of CSCs is a crucial area of research with the aim of developing novel therapeutic strategies to target this process and improve outcomes for individuals with cancer. Understanding the biological functions of exosomes derived from M2 macrophages and their involvement in cancer may lead to the formulation of novel diagnostic tools and treatments for this disease. By targeting M2 macrophages and the exosomes they secrete, promising prospects emerge for cancer treatment, given their substantial contribution to cancer development and progression. Further research is required to fully grasp the intricate interactions between CSCs, M2 macrophages and exosomes in cancer, and to identify fresh targets for cancer therapy. The present review explores the pivotal roles played by exosomes derived from M2 cells in maintaining the stem‑like properties of cancer cells.
    Keywords:  M2 macrophages; cancer stem cells; exosomes; therapeutic strategies; tumor progression
    DOI:  https://doi.org/10.3892/ijo.2023.5574
  5. Front Bioeng Biotechnol. 2023 ;11 1257186
    Breakthrough in large-scale production of iPSCs-derived exosomes to promote clinical applications.
    Xiaoxiao Chen, Ke Li, Jiangming Chen, Songwen Tan.
      
    Keywords:  3D culture; biogenesis; exosomes; iPSCs; large-scale production
    DOI:  https://doi.org/10.3389/fbioe.2023.1257186
  6. Am J Cancer Res. 2023 ;13(8): 3482-3499
    Colorectal cancer cell-secreted exosomal miRNA N-72 promotes tumor angiogenesis by targeting CLDN18.
    Ying Li, Di Jiang, Zhi-Xin Zhang, Jun-Jun Zhang, Hong-Yu He, Jian-Li Liu, Ting Wang, Xia-Xia Yang, Bang-Dong Liu, Li-Li Yang, Xiao Zhi, Xiao-Bei Zhang, Tian-Lun Li, Yan-Rong Liu.
      Angiogenesis is essential for the growth and metastasis of several malignant tumors including colorectal cancer (CRC). The molecular mechanism underlying CRC angiogenesis has not been fully elucidated. Emerging evidence indicates that secreted microRNAs (miRNAs) may mediate the intercellular communication between tumor cells and neighboring endothelial cells to regulate tumor angiogenesis. In addition, exosomes have been shown to carry and deliver miRNAs to regulate angiogenesis. miRNA N-72 is a novel miRNA that plays a regulatory role in the EGF-induced migration of human amnion mesenchymal stem cells. However, the relation between miRNA N-72 and cancer remains unclear. We here found that CRC cells could secrete miRNA N-72. A high miRNA N-72 level was detected in the serum of CRC patients and the cultured CRC cells. Moreover, the CRC cell-secreted miRNA N-72 could promote the migration, tubulogenesis, and permeability of endothelial cells. In addition, the mouse xenograft model was used to verify the facilitating effects of miRNA N-72 on CRC growth, angiogenesis, and metastasis in vivo. Further mechanism analysis revealed that CRC cell-secreted miRNA N-72 could be delivered into endothelial cells via exosomes, which then inhibited cell junctions of endothelial cells by targeting CLDN18 and consequently promoted angiogenesis. Our findings reveal a novel mechanism of CRC angiogenesis and highlight the potential of secreted miRNA N-72 as a therapeutic target and a biomarker for CRC.
    Keywords:  CLDN18; angiogenesis; colorectal cancer; exosomes; miRNA N-72
  7. J Extracell Vesicles. 2023 Sep;12(9): e12356
    Identification of the SNARE complex that mediates the fusion of multivesicular bodies with the plasma membrane in exosome secretion.
    Chuqi Liu, Dexiang Liu, Shen Wang, Lu Gan, Xiangliang Yang, Cong Ma.
      Exosomes play crucial roles in local and distant cellular communication and are involved in various physiological and pathological processes. Tumour-derived exosomes are pivotal to tumorigenesis, but the precise mechanisms underlying their secretion remain elusive. In particular, the SNARE proteins that mediate the fusion of multivesicular bodies (MVBs) with the plasma membrane (PM) in tumour cells are subject to debate. In this study, we identified syntaxin-4, SNAP-23, and VAMP-7 as the SNAREs responsible for exosome secretion in MCF-7 breast cancer cells and found that a SNARE complex consisting of these SNAREs can drive membrane fusion in vitro. Deletion of any of these SNAREs in MCF-7 cells did not affect MVB biogenesis and transportation, indicating their specific involvement in MVB-PM fusion. In addition, syntaxin-4, SNAP-23, and VAMP-7 play equivalent roles in exosome secretion in both HeLa cervical cancer cells and A375 melanoma cells, suggesting their conserved function in exosome secretion. Furthermore, deletion of VAMP-7 in 4T1 mammary carcinoma cells efficiently inhibited exosome secretion and led to significant attenuation of tumour growth and lung metastasis in mouse models, implying that VAMP-7 may hold promise as a novel therapeutic target for breast cancer.
    Keywords:  SNARE; breast cancer; exosome secretion; membrane fusion; multivesicular bodies
    DOI:  https://doi.org/10.1002/jev2.12356
  8. PLoS One. 2023 ;18(9): e0291623
    Extracellular vesicles as a potential source of tumor-derived DNA in advanced pancreatic cancer.
    Morten Lapin, Kjersti Tjensvoll, Karoline Nedrebø, Eline Taksdal, Hans Janssen, Bjørnar Gilje, Oddmund Nordgård.
      Tumor-derived extracellular vesicles (EVs) are reported to contain nucleic acids, including DNA. Several studies have highlighted the potential of EV-derived DNA (evDNA) as a circulating biomarker, even demonstrating that evDNA can outperform cell-free DNA (cfDNA) in terms of sensitivity. Here, we evaluated EVs as a potential source of tumor-derived DNA in patients with advanced pancreatic cancer. evDNA from both DNase-treated and untreated EV samples was analyzed to determine whether the DNA was primarily located internally or outside (surface-bound) the EVs. To assess whether methodology affected the results, we isolated EVs using four different methods for small EV isolation and differential centrifugation for isolating large EVs. Our results indicated that the DNA content of EVs was significantly less than the cfDNA content isolated from the same plasma volume (p < 0.001). Most of the detected evDNA was also located on the outside of the vesicles. Furthermore, the fraction of tumor-derived DNA in EVs was similar to that found in cfDNA. In conclusion, our results suggest that quantification of evDNA, as a source of tumor-derived DNA, does not add information to that obtained with cfDNA, at least not in patients with advanced pancreatic cancer.
    DOI:  https://doi.org/10.1371/journal.pone.0291623
  9. Cureus. 2023 Aug;15(8): e43235
    MicroRNA Profiling in Circulating Exosomes in Oral Squamous Cell Carcinoma: A Systematic Review.
    Dinesh Y, Pratibha Ramani, Monal Yuwanati, Karthikeyan Ramalingam, Gheena S.
      Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer with several risk factors. Exosomes are extracellular vesicles generated by the fusion of multivesicular structures with the cell membrane and play an important role as intercellular messengers. MicroRNA (miRNA) is a noncoding RNA and regulates post-transcriptional modification. The present systematic review aims to identify and correlate the possible association and role of circulating exosomes with OSCC. Using the search strategy, articles fulfilling the inclusion criteria, published between January 2012 to March 2022, were retrieved from online databases including PubMed, Scopus, Web of Science, and Cochrane Library. About 904 articles were found using an electronic database and a human search. After reviewing the titles and abstracts, 614 studies were eliminated, and duplicate articles were removed. Five studies were included in this systematic review. Circulating exosomal expression of miRNA27, miRNA 21, and miRNA 155 showed significant upregulation in OSCC patients. Circulating exosomes could be potential biomarkers to be used in the detection of patients with OSCC. More studies are warranted in this area to gain a better understanding of the pathophysiology of OSCC and the function of molecular markers from circulating exosomes. Understanding the role of molecular markers from circulating exosomes in pathogenesis will provide a better understanding of the development of the disease, necessitating more study in this area. According to this review, circulating exosomes might be a potential approach to the identification of OSCC.
    Keywords:  circulating exosomes; microrna; oral potentially malignant disorders; oral squamous cell carcinoma; systematic review
    DOI:  https://doi.org/10.7759/cureus.43235
  10. Biomark Res. 2023 Sep 13. 11(1): 80
    Identification of exosomal microRNA panel as diagnostic and prognostic biomarker for small cell lung cancer.
    Dong Ha Kim, Hyojeong Park, Yun Jung Choi, Kyungtaek Im, Chae Won Lee, Da-Som Kim, Chan-Gi Pack, Hyun-Yi Kim, Chang-Min Choi, Jae Cheol Lee, Wonjun Ji, Jin Kyung Rho.
       BACKGROUND: Small cell lung cancer (SCLC) has an exceptionally poor prognosis; as most of the cases are initially diagnosed as extensive disease with hematogenous metastasis. Therefore, the early diagnosis of SCLC is very important and may improve its prognosis.
    METHODS: To investigate the feasibility of early diagnosis of SCLC, we examined exosomal microRNAs (miRNAs) present in serum obtained from patients with SCLC. First, exosomes were isolated in serum from patients with SCLC and healthy individuals and were characterized using particle size and protein markers. Additionally, miRNA array was performed to define SCLC-specific exosomal miRNAs. Second, the obtained miRNAs were further validated employing a large cohort. Finally, the ability to diagnose SCLC was estimated by area under the curve (AUC), and intracellular mRNA change patterns were verified through validated miRNAs.
    RESULTS: From the miRNA array results, we selected 51-miRNAs based on p-values and top 10 differentially expressed genes, and 25-miRNAs were validated using quantitative reverse transcription-polymerase chain reaction. The 25-miRNAs were further validated employing a large cohort. Among them, 7-miRNAs showed significant differences. Furthermore, 6-miRNAs (miR-3565, miR-3124-5p, miR-200b-3p, miR-6515, miR-3126-3p and miR-9-5p) were up-regulated and 1-miRNA (miR-92b-5p) was down-regulated. The AUC value of each miRNA sets between 0.64 and 0.76, however the combined application of 3-miRNAs (miR-200b-3p, miR-3124-5p and miR-92b-5p) remarkably improved the diagnostic value (AUC = 0.93). Gene ontology analysis revealed that the 3-miRNA panel is linked to various oncogene pathways and nervous system development. When the 3-miRNAs were introduced to cells, the resulting changes in total mRNA expression strongly indicated the presence of lung diseases, including lung cancer. In addition, the 3-miRNA panel was significantly associated with a poorer prognosis, although individual miRNAs have not been validated as prognostic markers.
    CONCLUSION: Our study identified SCLC-specific exosomal miRNAs, and the 3-miRNAs panel (miR-200b-3p, miR-3124-5p and miR-92b-5p) may serve as a diagnostic and prognostic marker for SCLC.
    Keywords:  Diagnosis; Exosomal miRNA; Exosome; Prognosis; SCLC
    DOI:  https://doi.org/10.1186/s40364-023-00517-1
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