bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2024‒05‒19
nine papers selected by
Muhammad Rizwan, COMSATS University
  1. Biological Roles and Clinical Applications of Exosomes in Breast Cancer: A Brief Review.
  2. Exosomal noncoding RNAs in gynecological cancers: implications for therapy resistance and biomarkers.
  3. Harnessing exosomes in theranostic applications: advancements and insights in gastrointestinal cancer research.
  4. The multifaceted role of extracellular vesicles (EVs) in colorectal cancer: metastasis, immune suppression, therapy resistance, and autophagy crosstalk.
  5. New roles of tumor-derived exosomes in tumor microenvironment.
  6. Human plasma derived exosomes: Impact of active and passive drug loading approaches on drug delivery.
  7. Stem cells derived exosomes as biological nano carriers for VCR sulfate for treating breast cancer stem cells.
  8. Tumor derived exosomal ENTPD2 impair CD8+ T cell function in colon cancer through ATP-adenosine metabolism reprogramming.
  9. Exosome-Mediated Paracrine Signaling Unveils miR-1246 as a Driver of Aggressiveness in Fusion-Negative Rhabdomyosarcoma.
  1. Int J Mol Sci. 2024 Apr 24. pii: 4620. [Epub ahead of print]25(9):
    Biological Roles and Clinical Applications of Exosomes in Breast Cancer: A Brief Review.
    Han Wang, Ruo Wang, Kunwei Shen, Renhong Huang, Zheng Wang.
      Breast cancer (BC) is a global health risk for women and has a high prevalence rate. The drug resistance, recurrence, and metastasis of BC affect patient prognosis, thus posing a challenge to scientists. Exosomes are extracellular vesicles (EVs) that originate from various cells; they have a double-layered lipid membrane structure and contain rich biological information. They mediate intercellular communication and have pivotal roles in tumor development, progression, and metastasis and drug resistance. Exosomes are important cell communication mediators in the tumor microenvironment (TME). Exosomes are utilized as diagnostic and prognostic biomarkers for estimating the treatment efficacy of BC and have the potential to function as tools to enable the targeted delivery of antitumor drugs. This review introduces recent progress in research on how exosomes influence tumor development and the TME. We also present the research progress on the application of exosomes as prognostic and diagnostic biomarkers and drug delivery tools.
    Keywords:  breast cancer; exosomes; extracellular vesicles; tumor microenvironment
    DOI:  https://doi.org/10.3390/ijms25094620
  2. Front Oncol. 2024 ;14 1349474
    Exosomal noncoding RNAs in gynecological cancers: implications for therapy resistance and biomarkers.
    Changfen Xu, Peiyao Xu, Jiaqi Zhang, Sheng He, Tingting Hua, Aiwu Huang.
      Gynecologic cancers, including ovarian cancer (OC), cervical cancer (CC), and endometrial cancer (EC), pose a serious threat to women's health and quality of life due to their high incidence and lethality. Therapeutic resistance in tumors refers to reduced sensitivity of tumor cells to therapeutic drugs or radiation, which compromises the efficacy of treatment or renders it ineffective. Therapeutic resistance significantly contributes to treatment failure in gynecologic tumors, although the specific molecular mechanisms remain unclear. Exosomes are nanoscale vesicles released and received by distinct kinds of cells. Exosomes contain proteins, lipids, and RNAs closely linked to their origins and functions. Recent studies have demonstrated that exosomal ncRNAs may be involved in intercellular communication and can modulate the progression of tumorigenesis, aggravation and metastasis, tumor microenvironment (TME), and drug resistance. Besides, exosomal ncRNAs also have the potential to become significant diagnostic and prognostic biomarkers in various of diseases. In this paper, we reviewed the biological roles and mechanisms of exosomal ncRNAs in the drug resistance of gynecologic tumors, as well as explored the potential of exosomal ncRNAs acting as the liquid biopsy molecular markers in gynecologic cancers.
    Keywords:  biomarkers; exosomes; gynecologic tumors; ncRNAs; targeted therapy
    DOI:  https://doi.org/10.3389/fonc.2024.1349474
  3. Discov Oncol. 2024 May 14. 15(1): 162
    Harnessing exosomes in theranostic applications: advancements and insights in gastrointestinal cancer research.
    Ali Shojaeian, S R Naeimi Torshizi, Mahsa Sadat Parsapasand, Zahra Sobhi Amjad, Ali Khezrian, Abbas Alibakhshi, Faye Yun, Kaveh Baghaei, Razieh Amini, Stevan Pecic.
      Exosomes are small extracellular vesicles (30-150 nm) that are formed by endocytosis containing complex RNA as well as protein structures and are vital in intercellular communication and can be used in gene therapy and drug delivery. According to the cell sources of origin and the environmental conditions they are exposed to, these nanovesicles are very heterogeneous and dynamic in terms of content (cargo), size and membrane composition. Exosomes are released under physiological and pathological conditions and influence the pathogenesis of cancers through various mechanisms, including angiogenesis, metastasis, immune dysregulation, drug resistance, and tumor growth/development. Gastrointestinal cancer is one of the deadliest types of cancer in humans and can involve organs e.g., the esophagus and stomach, or others such as the liver, pancreas, small intestine, and colon. Early diagnosis is very important in this field because the overall survival of patients is low due to diagnosis in late stages and recurrence. Also, various therapeutic strategies have failed and there is an unmet need for the new therapeutic agents. Exosomes can become promising candidates in gastrointestinal cancers as biomarkers and therapeutic agents due to their lower immunity and passing the main physiological barriers. In this work, we provide a general overview of exosomes, their biogenesis and biological functions. In addition, we discuss the potential of exosomes to serve as biomarkers, agents in cancer treatment, drug delivery systems, and effective vaccines in immunotherapy, with an emphasis on gastrointestinal cancers.
    Keywords:  Biomarker; Cancer therapy; Exosomes; Gastrointestinal cancer
    DOI:  https://doi.org/10.1007/s12672-024-01024-x
  4. J Transl Med. 2024 May 13. 22(1): 452
    The multifaceted role of extracellular vesicles (EVs) in colorectal cancer: metastasis, immune suppression, therapy resistance, and autophagy crosstalk.
    Soheil Rahmati, Aysan Moeinafshar, Nima Rezaei.
      Extracellular vesicles (EVs) are lipid bilayer structures released by all cells and widely distributed in all biological fluids. EVs are implicated in diverse physiopathological processes by orchestrating cell-cell communication. Colorectal cancer (CRC) is one of the most common cancers worldwide, with metastasis being the leading cause of mortality in CRC patients. EVs contribute significantly to the advancement and spread of CRC by transferring their cargo, which includes lipids, proteins, RNAs, and DNAs, to neighboring or distant cells. Besides, they can serve as non-invasive diagnostic and prognostic biomarkers for early detection of CRC or be harnessed as effective carriers for delivering therapeutic agents. Autophagy is an essential cellular process that serves to remove damaged proteins and organelles by lysosomal degradation to maintain cellular homeostasis. Autophagy and EV release are coordinately activated in tumor cells and share common factors and regulatory mechanisms. Although the significance of autophagy and EVs in cancer is well established, the exact mechanism of their interplay in tumor development is obscure. This review focuses on examining the specific functions of EVs in various aspects of CRC, including progression, metastasis, immune regulation, and therapy resistance. Further, we overview emerging discoveries relevant to autophagy and EVs crosstalk in CRC.
    Keywords:  Autophagy; Biomarkers; Colorectal cancer; Exosomes; Extracellular vesicles; Immune suppression; Metastasis; Therapy resistance; miRNAs
    DOI:  https://doi.org/10.1186/s12967-024-05267-8
  5. Chin J Cancer Res. 2024 Apr 30. 36(2): 151-166
    New roles of tumor-derived exosomes in tumor microenvironment.
    Shiqian Chen, Jinzhe Sun, Huan Zhou, Hongbin Lei, Dan Zang, Jun Chen.
      Throughout tumorigenesis, the co-evolution of tumor cells and their surrounding microenvironment leads to the development of malignant phenotypes. Cellular communication within the tumor microenvironment (TME) plays a critical role in influencing various aspects of tumor progression, including invasion and metastasis. The release of exosomes, a type of extracellular vesicle, by most cell types in the body, is an essential mediator of intercellular communication. A growing body of research indicates that tumor-derived exosomes (TDEs) significantly expedite tumor progression through multiple mechanisms, inducing epithelial-mesenchymal transition and macrophage polarization, enhancing angiogenesis, and aiding in the immune evasion of tumor cells. Herein, we describe the formation and characteristics of the TME, and summarize the contents of TDEs and their diverse functions in modulating tumor development. Furthermore, we explore potential applications of TDEs in tumor diagnosis and treatment.
    Keywords:  Tumor-derived exosomes; diagnosis; treatment; tumor microenvironment; tumorigenesis
    DOI:  https://doi.org/10.21147/j.issn.1000-9604.2024.02.05
  6. Saudi Pharm J. 2024 Jun;32(6): 102096
    Human plasma derived exosomes: Impact of active and passive drug loading approaches on drug delivery.
    Rabia Gul, Hamid Bashir, Muhammad Sarfraz, Ahson Jabbar Shaikh, Yousef A Bin Jardan, Zahid Hussain, Muhammad Hassham Hassan Bin Asad, Faisal Gulzar, Bo Guan, Imran Nazir, Muhammad Imran Amirzada.
      The aim of the current study was to explore the potential of human plasma-derived exosomes as versatile carriers for drug delivery by employing various active and passive loading methods. Exosomes were isolated from human plasma using differential centrifugation and ultrafiltration method. Drug loading was achieved by employing sonication and freeze thaw methods, facilitating effective drug encapsulation within exosomes for delivery. Each approach was examined for its effectiveness, loading efficiency and ability to preserve membrane stability. Methotrexate (MTX), a weak acid model drug was loaded at a concentration of 2.2 µM to exosomes underwent characterization using various techniques such as particle size analysis, transmission electron microscopy and drug loading capacity. Human plasma derived exosomes showed a mean size of 162.15 ± 28.21 nm and zeta potential of -30.6 ± 0.71 mV. These exosomes were successfully loaded with MTX demonstrated a better drug encapsulation of 64.538 ± 1.54 % by freeze thaw method in comparison 55.515 ± 1.907 % by sonication. In-vitro drug release displayed 60 % loaded drug released within 72 h by freeze thaw method that was significantly different from that by sonication method i.e., 99 % within 72 h (p value 0.0045). Moreover, cell viability of exosomes loaded by freeze thaw method was significantly higher than that by sonication method (p value 0.0091) suggested that there was membrane disruption by sonication method. In conclusion, this study offers valuable insights into the potential of human plasma-derived exosomes loaded by freeze thaw method suggest as a promising carrier for improved drug loading and maintenance of exosomal membrane integrity.
    Keywords:  Drug loading capacity; Exosomal integrity; Freeze thaw method; Human Plasma derived exosomes; Ultrasonication
    DOI:  https://doi.org/10.1016/j.jsps.2024.102096
  7. Sci Rep. 2024 05 14. 14(1): 10964
    Stem cells derived exosomes as biological nano carriers for VCR sulfate for treating breast cancer stem cells.
    Ahmed H Farouk, Ahmed Aref, Belal A Fathy, Ahmed N Abdallah.
      Due to vincristine sulfate's (VCR sulfate) toxicity and non-specific targeting, which might adversely damage healthy cells, its clinical application is restricted. In this study, we loaded VCR sulfate on exosomes generated from mesenchymal stem cells (MSCs) to enhance its targeted distribution. Exosomes are able to deliver molecules to specific cells and tissues and have therapeutic potential. In this study, we isolated exosomes from MSCs, and using probe-sonication approach loaded them with VCR sulfate. Using SRB assay, the cytotoxicity of VCR sulfate-Exo was assessed in T47D breast cancer cells, and the results were contrasted with those of free VCR sulfate. Then We labeled markers (CD44+/CD24-) in the cell line to assess the targeting effectiveness of VCR sulfate-Exo using flow cytometry. Our results showed that the cytotoxicity of VCR sulfate-Exo was nearly the same as that of VCR sulfate. Flow cytometry analysis revealed that VRC sulfate-Exo was more effectively targeted to MSCs than free VCR sulfate. Our study shows that loading VCR sulfate to MSCs-derived exosomes can improve their targeted delivery and lessen their side effects. Additional research is required to determine VCR sulfate-Exo's in vivo effectiveness and safety and improve the loading and delivery strategies.
    DOI:  https://doi.org/10.1038/s41598-024-59736-7
  8. Cell Commun Signal. 2024 May 16. 22(1): 274
    Tumor derived exosomal ENTPD2 impair CD8+ T cell function in colon cancer through ATP-adenosine metabolism reprogramming.
    Mengchen Shi, Linsen Ye, Lu Zhao, Lingyuan He, Junxiong Chen, Jingdan Zhang, Yixi Su, Haiyan Dong, Jiaqi Liu, Liumei Liang, Wenwen Zheng, Yanhong Xiao, Huanliang Liu, Xiangling Yang, Zihuan Yang.
      BACKGROUND: Extracellular ATP-AMP-adenosine metabolism plays a pivotal role in modulating tumor immune responses. Previous studies have shown that the conversion of ATP to AMP is primarily catalysed by Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1/CD39), a widely studied ATPase, which is expressed in tumor-associated immune cells. However, the function of ATPases derived from tumor cells themselves remains poorly understood. The purpose of this study was to investigate the role of colon cancer cell-derived ATPases in the development and progression of colon cancer.METHODS: Bioinformatic and tissue microarray analyses were performed to investigate the expression of ATPase family members in colon cancer. An ATP hydrolysis assay, high-performance liquid chromatography (HPLC), and CCK8 and colony formation assays were used to determine the effects of ENTPD2 on the biological functions of colon cancer cells. Flow cytometric and RNA-seq analyses were used to explore the function of CD8+ T cells. Immunoelectron microscopy and western blotting were used to evaluate the expression of ENTPD2 in exosomes. Double-labelling immunofluorescence and western blotting were used to examine the expression of ENTPD2 in serum exosomes and colon cancer tissues.
    RESULTS: We found that ENTPD2, rather than the well-known ATPase CD39, is highly expressed in cancer cells and is significantly positively associated with poor patient prognosis in patients with colon cancer. The overexpression of ENTPD2 in cancer cells augmented tumor progression in immunocompetent mice by inhibiting the function of CD8+ T cells. Moreover, ENTPD2 is localized primarily within exosomes. On the one hand, exosomal ENTPD2 reduces extracellular ATP levels, thereby inhibiting P2X7R-mediated NFATc1 nuclear transcription; on the other hand, it facilitates the increased conversion of ATP to adenosine, hence promoting adenosine-A2AR pathway activity. In patients with colon cancer, the serum level of exosomal ENTPD2 is positively associated with advanced TNM stage and high tumor invasion depth. Moreover, the level of ENTPD2 in the serum exosomes of colon cancer patients is positively correlated with the ENTPD2 expression level in paired colon cancer tissues, and the ENTPD2 level in both serum exosomes and tissues is significantly negatively correlated with the ENTPD2 expression level in tumor-infiltrating CD8+ T cells.
    CONCLUSION: Our study suggests that exosomal ENTPD2, originated from colon cancer cells, contributes to the immunosuppressive microenvironment by promoting ATP-adenosine metabolism. These findings highlight the importance of exosome-derived hydrolytic enzymes as independent entities in shaping the tumor immune microenvironment.
    Keywords:  Adenosine; CD8+ T cell; Colon cancer; Ectonucleoside triphosphate diphosphohydrolase; Exosome
    DOI:  https://doi.org/10.1186/s12964-024-01654-2
  9. Cancers (Basel). 2024 Apr 25. pii: 1652. [Epub ahead of print]16(9):
    Exosome-Mediated Paracrine Signaling Unveils miR-1246 as a Driver of Aggressiveness in Fusion-Negative Rhabdomyosarcoma.
    Farah Ramadan, Raya Saab, Farah Ghamloush, Rita Khoueiry, Zdenko Herceg, Ludovic Gomez, Bassam Badran, Philippe Clezardin, Nader Hussein, Pascale A Cohen, Sandra E Ghayad.
      Rhabdomyosarcoma is a pediatric cancer associated with aggressiveness and a tendency to develop metastases. Fusion-negative rhabdomyosarcoma (FN-RMS) is the most commonly occurring subtype of RMS, where metastatic disease can hinder treatment success and decrease survival rates. RMS-derived exosomes were previously demonstrated to be enriched with miRNAs, including miR-1246, possibly contributing to disease aggressiveness. We aimed to decipher the functional impact of exosomal miR-1246 on recipient cells and its role in promoting aggressiveness. Treatment of normal fibroblasts with FN-RMS-derived exosomes resulted in a significant uptake of miR-1246 paired with an increase in cell proliferation, migration, and invasion. In turn, delivery of miR-1246-mimic lipoplexes promoted fibroblast proliferation, migration, and invasion in a similar manner. Conversely, when silencing miR-1246 in FN-RMS cells, the resulting derived exosomes demonstrated reversed effects on recipient cells' phenotype. Delivery of exosomal miR-1246 targets GSK3β and promotes β-catenin nuclear accumulation, suggesting a deregulation of the Wnt pathway, known to be important in tumor progression. Finally, a pilot clinical study highlighted, for the first time, the presence of high exosomal miR-1246 levels in RMS patients' sera. Altogether, our results demonstrate that exosomal miR-1246 has the potential to alter the tumor microenvironment of FN-RMS cells, suggesting its potential role in promoting oncogenesis.
    Keywords:  Rhabdomyosarcoma; aggressiveness; exosomes; fusion-negative RMS; miR-1246; paracrine signaling
    DOI:  https://doi.org/10.3390/cancers16091652
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