bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2024–12–29
nine papers selected by
Muhammad Rizwan, COMSATS University
  1. Exosomes, their sources, and possible uses in cancer therapy in the era of personalized medicine.
  2. Exosomal signaling in cancer metastasis: Molecular insights and therapeutic opportunities.
  3. Tumor-derived exosomes: Unravelling the pathogenesis of pancreatic cancer with liver metastases and exploring the potential for clinical translation.
  4. Exosome-driven nano-immunotherapy: revolutionizing colorectal cancer treatment.
  5. Liquid biopsies and exosomal ncRNA: Transforming pancreatic cancer diagnostics and therapeutics.
  6. The effect of cancer cell-derived exosomal proteins on macrophage polarization: An in-depth review.
  7. Exosome-derived proteins in gastric cancer progression, drug resistance, and immune response.
  8. Exosome-mediated delivery of CRISPR-Cas9: A revolutionary approach to cancer gene editing.
  9. Exosomal ANXA2 facilitates ovarian cancer peritoneal metastasis by activating peritoneal mesothelial cells through binding with TLR2.
  1. J Cancer Res Clin Oncol. 2024 Dec 26. 151(1): 16
    Exosomes, their sources, and possible uses in cancer therapy in the era of personalized medicine.
    Tomas Zemanek, Lubos Danisovic, Andreas Nicodemou.
      Despite significant advances in immunotherapy, its efficacy in solid tumors remains limited. Exosomes, a primary type of extracellular vesicles, can transport diverse intracellular molecules to nearby or distant cells and organs, facilitating numerous biological functions. Research has shown that exosomes have the dual ability to both activate and suppress the immune system. Their potential as anticancer vaccines arise from the capacity to carry antigens and major histocompatibility complex (MHC) molecules. Exosomes derived from blood, saliva, urine, and cerebrospinal fluid serve as promising biomarkers for cancer diagnosis and prognosis. Recent advancements in exosome-based therapy have highlighted its utility in drug delivery and immunotherapy. This review examines the composition and sources of exosomes within the immune microenvironment of solid tumors and delves into the mechanisms and pathways through which exosomes impact immunotherapy. We further explore the clinical potential of engineered exosomes and exosome vaccines in solid tumor immunotherapy. These insights may pave the way for exosome-based strategies in cancer diagnosis, treatment, and prognosis, enhancing the effectiveness of immunotherapy for solid tumors.
    Keywords:  Cancer; Cell therapy; Exosomes; Immunotherapy; Personalized medicine; Tumor
    DOI:  https://doi.org/10.1007/s00432-024-06066-w
  2. Arch Biochem Biophys. 2024 Dec 19. pii: S0003-9861(24)00399-0. [Epub ahead of print]764 110277
    Exosomal signaling in cancer metastasis: Molecular insights and therapeutic opportunities.
    Manasi S Pote, Rajesh N Gacche.
      Exosomes are membrane-bound extracellular vesicles that play a role in exchanging biological products across membranes and serve as intermediaries in intercellular communication to maintain normal homeostasis. Numerous molecules, including lipids, proteins, and nucleic acids are enclosed in exosomes. Exosomes are constantly released into the extracellular environment and exhibit distinct characteristics based on the secreted cells that produce them. Exosome-mediated cell-to-cell communication has reportedly been shown to affect multiple cancer hallmarks, such as immune response modulation, pre-metastatic niche formation, angiogenesis, stromal cell reprogramming, extracellular matrix architecture remodeling, or even drug resistance, and eventually the development and metastasis of cancer cells. Exosomes can be used as therapeutic targets and possible diagnostic biomarkers by selectively loading oncogenic molecules into them. We highlight the important roles that exosomes play in cancer development in this review, which may lead to the development of fresh approaches for future clinical uses.
    Keywords:  Angiogenesis; Exosomes; Pre-metastatic niche; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.abb.2024.110277
  3. Cancer Lett. 2024 Dec 19. pii: S0304-3835(24)00798-5. [Epub ahead of print]611 217403
    Tumor-derived exosomes: Unravelling the pathogenesis of pancreatic cancer with liver metastases and exploring the potential for clinical translation.
    Dongqi Li, Xiangyu Chu, Yongsu Ma, Fusheng Zhang, Xiaodong Tian, Yanlian Yang, Yinmo Yang.
      Pancreatic cancer (PC) is one of the most malignant solid cancers, and PC metastasis, particularly liver metastasis, is a major cause of cancer mortality. A key event in tumor metastasis is the formation of pre-metastatic niche (PMN), which provides a microenvironment conducive to tumor cells colonization and progression. Various molecules loaded in tumor-derived exosomes (TDEs) contribute to PMN formation and distant tumor metastasis, by regulating immune and stromal cell function, inducing angiogenesis, and promoting metabolic reprogramming. Therefore, therapies targeting PMN may offer novel advantages to prevent tumor metastasis at an earlier stage. In this review, we summarize multifaceted mechanisms underlying hepatic PMN formation, with a focus on how PC TDEs participate in angiogenesis and vascular permeability, create immune suppressive microenvironment, remodel the extracellular matrix, and regulate metabolic reprogramming. In addition, we highlight the promise of TDEs for early diagnosis and effective therapy of PC liver metastases.
    Keywords:  Liquid biopsy; Liver metastasis; Pancreatic cancer; Pre-metastatic niche; Tumor-derived exosomes
    DOI:  https://doi.org/10.1016/j.canlet.2024.217403
  4. Mol Biol Rep. 2024 Dec 26. 52(1): 83
    Exosome-driven nano-immunotherapy: revolutionizing colorectal cancer treatment.
    Masoud Lahouty, Manouchehr Fadaee, Dariush Shanehbandi, Tohid Kazemi.
      Colorectal cancer (CRC) ranks as the third most common cancer worldwide and remains a major cause of cancer-related deaths, necessitating the development of innovative therapeutic approaches beyond conventional treatment modalities. Conventional therapies, such as radiation, chemotherapy, and surgery, are hindered by challenges like imprecise targeting, substantial toxicity, and the development of resistance. Exosome-driven nano-immunotherapy has emerged as a groundbreaking approach that leverages the natural properties of exosomes-cell-derived vesicles known for their role in intercellular communication-to deliver therapeutic agents with high precision and specificity. This approach utilizes the natural ability of exosomes to serve as natural nanocarriers for various biomolecules, such as proteins, nucleic acids, and lipids, enabling precise drug delivery and immune modulation. Exosomes offer distinct advantages compared to traditional drug delivery systems, including their biocompatibility, capability to traverse biological barriers, and suitability for personalized medicine approaches. We evaluate the effectiveness of exosome-based therapies in comparison to traditional approaches, emphasizing their ability to achieve precise delivery, minimize systemic toxicity, and enhance treatment results. Despite their promise, several challenges remain, including the standardization of exosome isolation and production, optimization of cargo loading techniques, and ensuring safety and efficacy in clinical applications. By overcoming these obstacles and leveraging the distinctive characteristics of exosomes, exosome-driven nano-immunotherapy presents a promising avenue for more efficient therapeutic interventions.
    Keywords:  Colon cancer; Drug resistance; Extracellular vesicles; Nanoparticles; Novel immunotherapy
    DOI:  https://doi.org/10.1007/s11033-024-10157-9
  5. Clin Chim Acta. 2024 Dec 18. pii: S0009-8981(24)02358-1. [Epub ahead of print]567 120105
    Liquid biopsies and exosomal ncRNA: Transforming pancreatic cancer diagnostics and therapeutics.
    Ashok Kumar Balaraman, Ehssan Moglad, Muhammad Afzal, M Arockia Babu, Kavita Goyal, R Roopashree, Irwanjot Kaur, Sachin Kumar, MRavi Kumar, Ashish Singh Chauhan, S Hemalatha, Gaurav Gupta, Haider Ali.
      Pancreatic cancer is a highly fatal malignancy due to poor early detection rate and resistance to conventional therapies. This review examines the potential for liquid biopsy as a transformative technology to identify diagnostic and therapeutic targets in pancreatic cancer. Specifically, we explore emerging biomarkers such as exosomal non-coding RNAs (ncRNAs), circulating tumor DNA (ctDNA), and circulating tumor cells (CTCs). Tumor-derived exosomes contain nucleic acid and protein that reflect the unique molecular landscape of the malignancy and can serve as an alternative diagnostic approach vs traditional biomarkers like CA19-9. Herein we highlight exosomal miRNAs, lncRNAs, and other ncRNAs alongside ctDNA and CTC-based strategies, evaluating their combined ability to improve early detection, disease monitoring and treatment response. Furthermore, the therapeutic implications of ncRNAs such as lncRNA UCA1 and miR-3960 in chemoresistance and progression are also discussed via suppression of EZH2 and PTEN/AKT pathways. Emerging therapeutic strategies that target the immune response, epithelial-mesenchymal transition (EMT) and drug resistance are explored. This review demonstrates a paradigm shift in pancreatic cancer management toward personalized, less invasive and more effective approaches.
    Keywords:  Biomarkers; Liquid Biopsies; Pancreatic cancer; lncRNAs; miRNAs; ncRNAs
    DOI:  https://doi.org/10.1016/j.cca.2024.120105
  6. Exp Cell Res. 2024 Dec 20. pii: S0014-4827(24)00484-1. [Epub ahead of print]444(2): 114393
    The effect of cancer cell-derived exosomal proteins on macrophage polarization: An in-depth review.
    Khandu Wadhonkar, Soumalya Das, Ramachandran Subramanian, Mobbassar Hassan Sk, Yashi Singh, Mirza S Baig.
      Cancer is characterized by unregulated cell proliferation, enabling it to invade and spread to different organs and tissues in the body. Cancer progression is intricately influenced by the complex dynamics within the tumor microenvironment (TME). The TME is a composite and dynamic network comprising cancer cells and various immune cells, including tumor-associated macrophages. Exosomes facilitate the communication between different cancer cells as well as other types of cells. This review particularly focuses on exosomal proteins derived from different cancer cells in mounting the complex crosstalk between cells of cancer and macrophages within the TME. Most cancer-derived exosomal proteins polarize macrophages towards M2 phenotype, promoting cancer aggressiveness, while a few have role switching towards the M1 phenotype, inhibiting cancer proliferation, respectively. In this review, we summarize, for the first time, the dual impact of cancer cell-derived exosomal proteins on macrophage polarization and the associated signaling pathways, offering valuable insights for developing innovative therapeutic strategies against diverse cancer types.
    Keywords:  Cancer; Cell signaling; Exosomal proteins; Macrophage polarization; Tumor microenvironment (TME)
    DOI:  https://doi.org/10.1016/j.yexcr.2024.114393
  7. Cell Mol Biol Lett. 2024 Dec 24. 29(1): 157
    Exosome-derived proteins in gastric cancer progression, drug resistance, and immune response.
    Jiayu Wang, Huan Zhang, Juntao Li, Xiangyu Ni, Wenying Yan, Yueqiu Chen, Tongguo Shi.
      Gastric cancer (GC) represents a prevalent malignancy globally, often diagnosed at advanced stages owing to subtle early symptoms, resulting in a poor prognosis. Exosomes are extracellular nano-sized vesicles and are secreted by various cells. Mounting evidence indicates that exosomes contain a wide range of molecules, such as DNA, RNA, lipids, and proteins, and play crucial roles in multiple cancers including GC. Recently, with the rapid development of mass spectrometry-based detection technology, researchers have paid increasing attention to exosomal cargo proteins. In this review, we discussed the origin of exosomes and the diagnostic and prognostic roles of exosomal proteins in GC. Moreover, we summarized the biological functions of exosomal proteins in GC processes, such as proliferation, metastasis, drug resistance, stemness, immune response, angiogenesis, and traditional Chinese medicine therapy. In summary, this review synthesizes current advancements in exosomal proteins associated with GC, offering insights that could pave the way for novel diagnostic and therapeutic strategies for GC in the foreseeable future.
    Keywords:  Biomarker; Drug resistance; Exosomal protein; Exosome; Gastric cancer; Immune response; Therapy
    DOI:  https://doi.org/10.1186/s11658-024-00676-5
  8. Pathol Res Pract. 2024 Dec 19. pii: S0344-0338(24)00696-4. [Epub ahead of print]266 155785
    Exosome-mediated delivery of CRISPR-Cas9: A revolutionary approach to cancer gene editing.
    Ashok Kumar Balaraman, M Arockia Babu, Ehssan Moglad, Viralkumar Mandaliya, M M Rekha, Sofia Gupta, G V Siva Prasad, Mukesh Kumari, Ashish Singh Chauhan, Haider Ali, Kavita Goyal.
      Several molecular strategies based on targeted gene delivery systems have been developed in recent years; however, the CRISPR-Cas9 technology introduced a new era of targeted gene editing, precisely modifying oncogenes, tumor suppressor genes, and other regulatory genes involved in carcinogenesis. However, efficiently and safely delivering CRISPR-Cas9 to cancer cells across the cell membrane and the nucleus is still challenging. Using viral vectors and nanoparticles presents issues of immunogenicity, off-target effects, and low targeting affinity. Naturally, extracellular vesicles called exosomes have garnered the most attention as delivery vehicles in oncology-related CRISPR-Cas9 calls due to their biocompatibility, loading capacity, and inherent targeting features. The following review discusses the current progress in using exosomes to deliver CRISPR-Cas9 components, the approaches to load the CRISPR components into exosomes, and the modification of exosomes to increase stability and tumor-targeted delivery. We discuss the latest strategies in targeting recently accomplished in the exosome field, including modifying the surface of exosomes to enhance their internalization by cancer cells, as well as the measures taken to overcome the impacts of TME on delivery efficiency. Focusing on in vitro and in vivo experimentation, this review shows that exosome-mediated CRISPR-Cas9 can potentially treat cancer types, including pancreatic, lymphoma, and leukemia, for given gene targets. This paper compares exosome-mediated delivery and conventional vectors regarding safety, immune response, and targeting ability. Last but not least, we present the major drawbacks and potential development of the seemingly promising field of exosome engineering in gene editing, with references to CRISPR technologies and applications that may help make the target exosomes therapeutic in oncology.
    Keywords:  Cancer therapy; Exosome engineering; Exosome-mediated delivery; Tumor microenvironment; Tumor-specific targeting
    DOI:  https://doi.org/10.1016/j.prp.2024.155785
  9. Cell Commun Signal. 2024 Dec 21. 22(1): 616
    Exosomal ANXA2 facilitates ovarian cancer peritoneal metastasis by activating peritoneal mesothelial cells through binding with TLR2.
    Jingni Zhang, Hongmei Liu, Qiulei Wu, Tong Liu, Xiaoli Liu, Jing Cai, Xiaoqing Yi, Zehua Wang, Lingling Gao.
       BACKGROUND: Peritoneal dissemination of ovarian cancer (OvCa) can be largely attributed to the formation of a metastatic microenvironment driven by tumoral exosomes. Here, we aimed to elucidate the mechanisms through which exosomal annexin A2 (ANXA2) derived from OvCa cells induces an HPMC phenotypic shift in favour of peritoneal metastasis.
    METHODS: Immunohistochemistry and orthotopic and intraperitoneal OvCa xenograft mouse models were used to clarify the relationship between tumour ANXA2 expression and peritoneal metastasis. Exosomes were isolated from OvCa cell lines via ultracentrifugation. Functional experiments on cell proliferation and motility, and western blot were performed to investigate the activation of HPMCs and its impact on tumour cell in vitro. High-throughput transcriptional sequencing and rescue experiments in which ANXA2 inhibitor (LCKLSL) or the toll-like receptor 2 (TLR2) inhibitor (C29) was used to co-culture the HPMCs with exosome were employed to identify the crucial functional molecules through which exosomal ANXA2 activates HPMCs. The impact of exosomal ANXA2-activated HPMCs on tumour progression was assessed via functional experiments.
    RESULTS: Primary OvCa samples with high ANXA2 expression exhibited a stronger tendency to metastasize to the abdominal cavity. Tumoral ANXA2 promoted OvCa peritoneal metastasis through the secretion of exosomes carrying ANXA2. ANXA2-loaded exosomes activated HPMCs through exosomal ANXA2 binding to TLR2, shifting the phenotype of HPMCs towards mesenchymal cells, increasing their migration and invasion capacities, and elevating the expression of lipocalin 2 (LCN2). High LCN2 expression in HPMCs promoted OvCa cell adhesion, proliferation, motility, and lipid metabolism reprogramming.
    CONCLUSION: Exosomal ANXA2 secreted by tumour cells activates HPMCs and induces the expression of LCN2, which in turn promotes the peritoneal metastasis of OvCa.
    Keywords:  Annexin A2; Exosome; Human peritoneal mesothelial cell; Lipocalin 2; Ovarian cancer; Toll-like receptor 2
    DOI:  https://doi.org/10.1186/s12964-024-01987-y
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