bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2023–10–29
seven papers selected by
Muhammad Rizwan, COMSATS University
  1. Exosomes in Cancer Progression and Therapy Resistance: Molecular Insights and Therapeutic Opportunities.
  2. The effects of intracellular and exosomal ncRNAs on cancer progression.
  3. Circulating exosomal miRNAs as a promising diagnostic biomarker in cancer.
  4. Extracellular vesicles as novel drug delivery systems to target cancer and other diseases: Recent advancements and future perspectives.
  5. Exosomal Non-coding RNAs: A New Approach to Melanoma Diagnosis and Therapeutic Strategy.
  6. Exosomal lncRNA NEAT1 inhibits NK cell activity to promote multiple myeloma cell immune escape via an EZH2/PBX1 axis.
  7. Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-β signaling.
  1. Life (Basel). 2023 Oct 09. pii: 2033. [Epub ahead of print]13(10):
    Exosomes in Cancer Progression and Therapy Resistance: Molecular Insights and Therapeutic Opportunities.
    Madita Wandrey, Jadwiga Jablonska, Roland H Stauber, Désirée Gül.
      The development of therapy resistance still represents a major hurdle in treating cancers, leading to impaired treatment success and increased patient morbidity. The establishment of minimally invasive liquid biopsies is a promising approach to improving the early diagnosis, as well as therapy monitoring, of solid tumors. Because of their manifold functions in the tumor microenvironment, tumor-associated small extracellular vesicles, referred to as exosomes, have become a subject of intense research. Besides their important roles in cancer progression, metastasis, and the immune response, it has been proposed that exosomes also contribute to the acquisition and transfer of therapy resistance, mainly by delivering functional proteins and RNAs, as well as facilitating the export of active drugs or functioning as extracellular decoys. Extensive research has focused on understanding the molecular mechanisms underlying the occurrence of resistance and translating these into strategies for early detection. With this review, we want to provide an overview of the current knowledge about the (patho-)biology of exosomes, as well as state-of-the-art methods of isolation and analysis. Furthermore, we highlight the role of exosomes in tumorigenesis and cancer treatment, where they can function as therapeutic agents, biomarkers, and/or targets. By focusing on their roles in therapy resistance, we will reveal new paths of exploiting exosomes for cancer diagnosis and treatment.
    Keywords:  cancer; cancer therapy; exosomes; resistance transmission; therapy resistance
    DOI:  https://doi.org/10.3390/life13102033
  2. Cancer Gene Ther. 2023 Oct 26.
    The effects of intracellular and exosomal ncRNAs on cancer progression.
    Yang-Hsiang Lin.
      Altered gene expression as well as mislocalization of a gene's encoded product (proteins or noncoding RNAs (ncRNAs)) can lead to disease and cancer formation. Multiple studies have indicated that exosomes and their contents act as cell-to-cell communicators and play a key role in cancer progression. Moreover, exosomes contain several functional molecules, including ncRNAs. NcRNAs function as master regulators to coordinate cell growth, cell motility and drug resistance. However, intracellular ncRNAs, which can be transferred to recipient cells via exosomes (exosomal ncRNAs), mediate common/distinct downstream molecules, signaling pathways and functions that are less emphasized concepts in cancer development research. In this study, by using exosomes as a model, we comprehensively discuss the current knowledge regarding (1) the functional role of ncRNAs, both their intracellular and exosomal forms, in cancer progression, (2) the possible mechanism of ncRNA incorporation into exosomes and (3) the therapeutic applications and limitations of exosomes based on current knowledge.
    DOI:  https://doi.org/10.1038/s41417-023-00679-y
  3. Physiol Res. 2023 Oct 27. 72(S3): S193-S207
    Circulating exosomal miRNAs as a promising diagnostic biomarker in cancer.
    R Lohajová Behulová, A Bugalová, J Bugala, E Struhárňanská, M Šafranek, I Juráš.
      Cancer belongs to multifactorial diseases characterized by uncontrolled growth and proliferation of abnormal cells. Breast cancer, non-small cell lung cancer, and colorectal cancer are the most frequently diagnosed malignancies with a high mortality rate. These carcinomas typically contain multiple genetically distinct subpopulations of tumor cells leading to tumor heterogeneity, which promotes the aggressiveness of the disease. Early diagnosis is necessary to increase patient progression-free survival. Particularly, miRNAs present in exosomes derived from tumors represent potential biomarkers suitable for early cancer diagnosis. Identification of miRNAs by liquid biopsy enables a personalized approach with the subsequent better clinical management of patients. This review article highlights the potential of circulating exosomal miRNAs in early breast, non-small cell lung, and colorectal cancer diagnosis.
  4. F1000Res. 2023 ;12 329
    Extracellular vesicles as novel drug delivery systems to target cancer and other diseases: Recent advancements and future perspectives.
    Divya Ramesh, Shankar Bakkannavar, Vinutha R Bhat, Krishna Sharan.
      Extracellular vesicles (EVs) are lipid-bound vesicles produced into the extracellular space by cells. Apoptotic bodies (ApoBD), microvesicles (MVs), and exosomes are examples of EVs, which act as essential regulators in cell-cell communication in both normal and diseased conditions. Natural cargo molecules such as miRNA, messenger RNA, and proteins are carried by EVs and transferred to nearby cells or distant cells through the process of circulation. Different signalling cascades are then influenced by these functionally active molecules. The information to be delivered to the target cells depends on the substances within the EVs that also includes synthesis method. EVs have attracted interest as potential delivery vehicles for therapies due to their features such as improved circulation stability, biocompatibility, reduced immunogenicity, and toxicity. Therefore, EVs are being regarded as potent carriers of therapeutics that can be used as a therapeutic agent for diseases like cancer. This review focuses on the exosome-mediated drug delivery to cancer cells and the advantages and challenges of using exosomes as a carrier molecule.
    Keywords:  ; Exosomes; Signalling cascade; Biocompatibility; Biogenesis;Cancer; EXTRACELLULAR VESICLES
    DOI:  https://doi.org/10.12688/f1000research.132186.1
  5. Curr Med Chem. 2023 Oct 24.
    Exosomal Non-coding RNAs: A New Approach to Melanoma Diagnosis and Therapeutic Strategy.
    Jie Liu, Xiaoping Hu, Wenqiang Xin, Xianbin Wang.
      Malignant melanoma (MM) is a highly aggressive cancer with a poor prognosis. Currently, although a variety of therapies are available for treating melanoma, MM is still a serious threat to the patient's life due to numerous factors, such as the recurrence of tumors, the emergence of drug resistance, and the lack of effective therapeutic agents. Exosomes are biologically active lipid-bilayer extracellular vesicles secreted by diverse cell types that mediate intercellular signal communication. Studies found that exosomes are involved in cancer by carrying multiple bioactive molecules, including non-- coding RNAs (ncRNAs). The ncRNAs have been reported to play an important role in regulating proliferation, angiogenesis, immune regulation, invasion, metastasis, and treatment resistance of tumors. However, the functional role of exosomal ncRNAs in MM remains unknown. Therefore, this review summarizes the current state of melanoma diagnosis, treatment, and the application of exosomal ncRNAs in MM patients, which may provide new insights into the mechanisms involved in melanoma progression and serve as biomarkers for diagnosis and therapeutic targets.
    Keywords:  Melanoma; biomarker; exosomes; non-coding RNAs; therapeutic targets
    DOI:  https://doi.org/10.2174/0109298673267553231017053329
  6. Mol Cancer Res. 2023 Oct 26.
    Exosomal lncRNA NEAT1 inhibits NK cell activity to promote multiple myeloma cell immune escape via an EZH2/PBX1 axis.
    Qing-Ming Wang, Guang-Yu Lian, Su-Mei Sheng, Jing Xu, Long-Long Ye, Chao Min, Shu-Fang Guo.
      Exosomal long noncoding RNAs (lncRNAs) derived from cancer cells are implicated in various processes, including cancer cell proliferation, metastasis, and immunomodulation. We investigated the role and underlying mechanism of exosome-transmitted lncRNA NEAT1 in the immune escape of multiple myeloma (MM) cells from natural killer (NK) cells. MM cells and samples from MM patients were obtained. The effects of MM cell-derived exosomes (MM exosomes) and exosomal NEAT1 on the functions of NK cells were evaluated using EdU staining, CCK-8, flow cytometry and ELISA. Chromatin and RNA immunoprecipitation were performed to identify interactions between NEAT1, enhancer of Zeste Homolog 2 (EZH2), and pre-B-cell leukemia transcription factor 1 (PBX1). A xenograft tumor model was constructed to verify the effects of exosomal NEAT1 on tumor growth. qRT-PCR, western blot and immunohistochemistry were conducted to detect related genes. NEAT1 levels were upregulated in MM tumor tissues, MM cells, and MM exosomes. MM exosomes suppressed cell proliferation, promoted apoptosis, reduced natural killer group 2, member D (NKG2D)-positive cells, and the production of tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ) in NK cells, whereas NEAT1-silenced exosomes had little effect. NEAT1 silenced PBX1 by recruiting EZH2. PBX1 knockdown abrogated the effects of NEAT1-silenced exosomes on NK and MM cells. NEAT1-silenced exosomes inhibited tumor growth in mice, decreased Ki67 and PD-L1, and increased NKG2D, TNF-α, and IFN-γ in tumor tissues. In summary, MM cell-derived exosomal NEAT1 suppressed NK cell activity by downregulating PBX1, promoting MM cell immune escape. This study suggests a potential strategy for treating MM. Implications: This study reveals that exosomal NEAT1 regulates EZH2/PBX1 axis to inhibit NK cell activity, thereby promoting multiple myeloma cell immune escape, which offers a novel therapeutic potential for MM.
    DOI:  https://doi.org/10.1158/1541-7786.MCR-23-0282
  7. Front Med. 2023 Oct 23.
    Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-β signaling.
    Yuanyuan Hao, Panpan Chen, Shanshan Guo, Mengyuan Li, Xueli Jin, Minghuan Zhang, Wenhai Deng, Ping Li, Wen Lei, Aibin Liang, Wenbin Qian.
      Tumor-derived exosomes (TEXs) enriched in immune suppressive molecules predominantly drive T-cell dysfunction and impair antitumor immunity. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for refractory and relapsed hematological malignancies, but whether lymphoma TEXs have the same impact on CAR T-cell remains unclear. Here, we demonstrated that B-cell lymphoma-derived exosomes induce the initial activation of CD19-CAR T-cells upon stimulation with exosomal CD19. However, lymphoma TEXs might subsequently induce CAR T-cell apoptosis and impair the tumor cytotoxicity of the cells because of the upregulated expression of the inhibitory receptors PD-1, TIM3, and LAG3 upon prolonged exposure. Similar results were observed in the CAR T-cells exposed to plasma exosomes from patients with lymphoma. More importantly, single-cell RNA sequencing revealed that CAR T-cells typically showed differentiated phenotypes and regulatory T-cell (Treg) phenotype conversion. By blocking transforming growth factor β (TGF-β)-Smad3 signaling with TGF-β inhibitor LY2109761, the negative effects of TEXs on Treg conversion, terminal differentiation, and immune checkpoint expression were rescued. Collectively, although TEXs lead to the initial activation of CAR T-cells, the effect of TEXs suppressed CAR T-cells, which can be rescued by LY2109761. A treatment regimen combining CAR T-cell therapy and TGF-β inhibitors might be a novel therapeutic strategy for refractory and relapsed B-cell lymphoma.
    Keywords:  TGF-β; chimeric antigen receptor T-cell; lymphoma; tumor-derived exosome
    DOI:  https://doi.org/10.1007/s11684-023-1010-1
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