bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2022–11–06
eight papers selected by
Muhammad Rizwan, COMSATS University
  1. The emerging role of exosomes in radiotherapy.
  2. Exosomes and mimics as novel delivery platform for cancer therapy.
  3. Mechanisms of function and clinical potential of exosomes in esophageal squamous cell carcinoma.
  4. Exosomal noncoding RNAs in prostate cancer.
  5. The role and underlying mechanisms of tumour-derived exosomes in lung cancer metastasis.
  6. Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer.
  7. Comparing Two Methods for the Isolation of Exosomes.
  8. An optimized exosome production strategy for enhanced yield while without sacrificing cargo loading efficiency.
  1. Cell Commun Signal. 2022 Oct 31. 20(1): 171
    The emerging role of exosomes in radiotherapy.
    Zhenyi Yang, Wen Zhong, Liang Yang, Ping Wen, Yixuan Luo, Chunli Wu.
      Presently, more than half of cancer patients receive radiotherapy to cure localized cancer, palliate symptoms, or control the progression of cancer. However, radioresistance and radiation-induced bystander effects (RIBEs) are still challenging problems in cancer treatment. Exosomes, as a kind of extracellular vesicle, have a significant function in mediating and regulating intercellular signaling pathways. An increasing number of studies have shown that radiotherapy can increase exosome secretion and alter exosome cargo. Furthermore, radiation-induced exosomes are involved in the mechanism of radioresistance and RIBEs. Therefore, exosomes hold great promise for clinical application in radiotherapy. In this review, we not only focus on the influence of radiation on exosome biogenesis, secretion and cargoes but also on the mechanism of radiation-induced exosomes in radioresistance and RIBEs, which may expand our insight into the cooperative function of exosomes in radiotherapy. Video abstract.
    Keywords:  Bystander effect; Exosomes; Radioresistance; Radiotherapy
    DOI:  https://doi.org/10.1186/s12964-022-00986-1
  2. Front Pharmacol. 2022 ;13 1001417
    Exosomes and mimics as novel delivery platform for cancer therapy.
    Fuxu Yang, Mingyue Wang, Xingang Guan.
      Exosomes are nano-sized biological extracellular vesicles transmitting information between cells and constituting a new intercellular communication mode. Exosomes have many advantages as an ideal drug delivery nanocarrier, including good biocompatibility, permeability, low toxicity, and low immunogenicity. Recently, exosomes have been used to deliver chemotherapeutic agents, natural drugs, nucleic acid drugs, and other antitumor drugs to treat many types of tumors. Due to the limited production of exosomes, synthetic exosome-mimics have been developed as an ideal platform for drug delivery. This review summarizes recent advances in the application of exosomes and exosome-mimics delivering therapeutic drugs in treating cancers.
    Keywords:  cancer therapy; drug delivery; exosome; nanovesicle; tumor targeting
    DOI:  https://doi.org/10.3389/fphar.2022.1001417
  3. Cancer Lett. 2022 Oct 31. pii: S0304-3835(22)00480-3. [Epub ahead of print] 215993
    Mechanisms of function and clinical potential of exosomes in esophageal squamous cell carcinoma.
    Lijun Zhao, Lili Yu, Xiangpeng Wang, Jangtao He, Xiaofei Zhu, Rui Zhang, Angang Yang.
      Esophageal squamous cell carcinoma (ESCC) remains one of the most lethal and widespread malignancies in China. Exosomes, a subset of tiny extracellular vesicles manufactured by all cells and present in all body fluids, contribute to intercellular communication and have become a focus of the search for new therapeutic strategies for cancer. A number of global analyses of exosome-mediated functions and regulatory mechanism in malignant diseases have recently been reported. There is extensive evidence that exosomes can be used as diagnostic and prognostic markers for cancer. However, our understanding of their clinical value and mechanisms of action in ESCC is still limited and has not been systematically reviewed. Here, we review current research specifically focused on the functions and mechanisms of action of ESCC tumor-derived exosomes and non-ESCC-derived exosomes in ESCC progression and describe opportunities and challenges in the clinical translation of exosomes.
    Keywords:  Biomarker; Drug delivery; Esophageal squamous cell carcinoma; Exosome; Novel therapies
    DOI:  https://doi.org/10.1016/j.canlet.2022.215993
  4. Clin Chim Acta. 2022 Oct 29. pii: S0009-8981(22)01352-3. [Epub ahead of print]537 127-132
    Exosomal noncoding RNAs in prostate cancer.
    Ahmad Movahedpour, Seyyed Hossein Khatami, Neda Karami, Omid Vakili, Parisa Naeli, Zeinab Jamali, Zahra Shabaninejad, Khalil Tazik, Hamid Behrouj, Hassan Ghasemi.
      Prostate cancer (PCa) is the second most common cancer and the fifth leading cause of mortality among men. The recurrent reports of false-positive results of common PCa biomarkers have led to the introduction of some promising biomarkers for PCa, such as exosomal non-coding RNAs (ncRNAs). Exosomes contain various components, such as several ncRNAs (miRNAs and lncRNAs), which are important in the initiation and progression of PCa. These ncRNAs also reflect the state of the origin cell. In this article, we reviewed research on the importance and roles of ncRNAs in PCa, focusing on exosomal ncRNAs. We highlighted plasma exosomal miRNAs (8 miRNAs), urine exosomal miRNAs (19miRNAs), serum miRNAs (2 miRNAs), and five miRNAs in semen used for PCa diagnosis. Also, four exosomal lncRNAs in plasma and urine can be used as biomarkers for PCa diagnosis.
    Keywords:  Biomarker; Diagnosis; Exosome; NcRNA; Prostate cancer
    DOI:  https://doi.org/10.1016/j.cca.2022.10.018
  5. Curr Opin Oncol. 2022 Nov 03.
    The role and underlying mechanisms of tumour-derived exosomes in lung cancer metastasis.
    Jinling He, Lingqi Yang, Ning Zhou, Lingling Zu, Song Xu.
       PURPOSE OF REVIEW: Lung cancer is one of the most common malignant tumours worldwide. Metastasis is a serious influencing factor for poor treatment effect and shortened survival in lung cancer. But the complicated underlying molecular mechanisms of tumour metastasis remain unclear. In this review, we aim to further summarize and explore the underlying mechanisms of tumour-derived exosomes (TDEs) in lung cancer metastasis.
    RECENT FINDINGS: TDEs are actively produced and released by tumour cells and carry messages from tumour cells to normal or abnormal cells residing at close or distant sites. Many studies have shown that TDEs promote lung cancer metastasis and development through multiple mechanisms, including epithelial-mesenchymal transition, immunosuppression and the formation of a premetastatic niche. TDEs regulate these mechanisms to promote metastasis by carrying DNA, proteins, miRNA, mRNA, lncRNA and ceRNA. Further exploring TDEs related to metastasis may be a promising treatment strategy and deserve further investigation.
    SUMMARY: Overall, TDEs play a critical role in metastatic of lung cancer. Further studies are needed to explore the underlying mechanisms of TDEs in lung cancer metastasis.
    DOI:  https://doi.org/10.1097/CCO.0000000000000913
  6. Mol Cancer. 2022 Nov 01. 21(1): 207
    Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer.
    Qing-Fang Han, Wen-Jia Li, Kai-Shun Hu, Jie Gao, Wen-Long Zhai, Jing-Hua Yang, Shui-Jun Zhang.
      Exosomes are well-known key mediators of intercellular communication and contribute to various physiological and pathological processes. Their biogenesis involves four key steps, including cargo sorting, MVB formation and maturation, transport of MVBs, and MVB fusion with the plasma membrane. Each process is modulated through the competition or coordination of multiple mechanisms, whereby diverse repertoires of molecular cargos are sorted into distinct subpopulations of exosomes, resulting in the high heterogeneity of exosomes. Intriguingly, cancer cells exploit various strategies, such as aberrant gene expression, posttranslational modifications, and altered signaling pathways, to regulate the biogenesis, composition, and eventually functions of exosomes to promote cancer progression. Therefore, exosome biogenesis-targeted therapy is being actively explored. In this review, we systematically summarize recent progress in understanding the machinery of exosome biogenesis and how it is regulated in the context of cancer. In particular, we highlight pharmacological targeting of exosome biogenesis as a promising cancer therapeutic strategy.
    Keywords:  Biogenesis; Cancer; Exosomes; Implications; Regulation
    DOI:  https://doi.org/10.1186/s12943-022-01671-0
  7. J Nucleic Acids. 2022 ;2022 8648373
    Comparing Two Methods for the Isolation of Exosomes.
    Mohammad A Aziz, Benedict Seo, Haizal M Hussaini, Merilyn Hibma, Alison M Rich.
      Exosomes are membrane-bound nanovesicles released by cells into their extracellular environment. They carry different types of RNA including mRNA which may be useful in the diagnosis of various diseases. Exosome isolation has been a challenge because of their small size; therefore, two exosome isolation methods were compared in this study. The Exoquick-TC PLUS™ exosome isolation kit (kit) was compared with the classic ultracentrifugation (UC) method for exosome isolation. In samples obtained using both methods, cryo-electron microscopy showed round or slightly elongated vesicles with diameters ranging from 50 to 150 nm and delimited by a bilayered membrane. Dynamic light scattering resulted in multiple peaks for kit exosomes, whereas a single peak was observed for UC exosomes. Significantly, more total RNA was present in UC exosomes in contrast to kit exosomes (P < 0.0001). This was reflected in subsequent mRNA analysis using qPCR, where UC exosomes had lower Ct values compared to kit exosomes. In conclusion, exosome characterization revealed the presence of exosomes in both UC and the kit samples. The kit samples presented additional peaks from DLS which might be due to impurities. Overall, due to a higher total RNA and mRNA content, UC is a better option for subsequent mRNA analysis; nevertheless, the kit can still be used if an ultracentrifuge is not available as four out of the five genes selected were detected and quantified using the kit.
    DOI:  https://doi.org/10.1155/2022/8648373
  8. J Nanobiotechnology. 2022 Oct 29. 20(1): 463
    An optimized exosome production strategy for enhanced yield while without sacrificing cargo loading efficiency.
    Rongxin Zhang, Te Bu, Ruidan Cao, Zhelong Li, Chen Wang, Bing Huang, Mengying Wei, Lijun Yuan, Guodong Yang.
       BACKGROUND: Exosome mediated mRNA delivery is a promising strategy for the treatment of multiple diseases. However, the low yield of exosomes is a bottleneck for clinical translation. In this study, we boosted exosome production via simultaneously reducing the expression of genes inhibiting exosome biogenesis and supplementing the culture medium with red cell membrane components.
    RESULTS: Among the candidate genes, knocking down of Rab4 was identified to have the highest efficacy in promoting exosome biogenesis while without any obvious cytotoxicity. Additionally, supplementing red cell membrane particles (RCMPs) in the culture medium further promoted exosome production. Combination of Rab4 knockdown and RCMP supplement increased exosome yield up to 14-fold. As a proof-of-concept study, low-density lipoprotein receptor (Ldlr) mRNA was forced expressed in the exosome donor cells and passively encapsulated into the exosomes during biogenesis with this strategy. Though exosome production per cell increased, the booster strategy didn't alter the loading efficiency of therapeutic Ldlr mRNA per exosome. Consistently, the therapeutic exosomes derived by the strategy alleviated liver steatosis and atherosclerosis in Ldlr-/- mice, similar as the exosomes produced by routine methods.
    CONCLUSIONS: Together, the proposed exosome booster strategy conquers the low yield bottleneck to some extent and would certainly facilitate the clinical translation of exosomes.
    Keywords:  Exosomes; Familial hypercholesterolemia; Red cell membrane; Yield; mRNA cargo
    DOI:  https://doi.org/10.1186/s12951-022-01668-3
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