bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2024–06–16
six papers selected by
Muhammad Rizwan, COMSATS University
  1. Tumor-associated macrophages derived exosomes; from pathogenesis to therapeutic opportunities.
  2. Exosomal miR-1228-5p down-regulates DUSP22 to promotes cell proliferation and migration in small cell lung cancer.
  3. Exosomal microRNAs in hepatocellular carcinoma, expanding research field.
  4. Dysregulation of exosomal miRNAs and their related genes in head and neck cancer patients.
  5. Exosomal mRNA Cargo are biomarkers of tumor and immune cell populations in pediatric osteosarcoma.
  6. Anti-BCMA-engineered Exosomes for Bortezomib Targeted Delivery in Multiple Myeloma.
  1. Int Immunopharmacol. 2024 Jun 07. pii: S1567-5769(24)00926-3. [Epub ahead of print]136 112406
    Tumor-associated macrophages derived exosomes; from pathogenesis to therapeutic opportunities.
    Sara Hadad, Amirreza Khalaji, Amirreza Jabbaripour Sarmadian, Pooneh Jabbaripour Sarmadian, Elham Mohebi Janagard, Behzad Baradaran.
      Tumor-associated macrophages (TAMs) exert profound influences on cancer progression, orchestrating a dynamic interplay within the tumor microenvironment. Recent attention has focused on the role of TAM-derived exosomes, small extracellular vesicles containing bioactive molecules, in mediating this intricate communication. This review comprehensively synthesizes current knowledge, emphasizing the diverse functions of TAM-derived exosomes across various cancer types. The review delves into the impact of TAM-derived exosomes on fundamental cancer hallmarks, elucidating their involvement in promoting cancer cell proliferation, migration, invasion, and apoptosis evasion. By dissecting the molecular cargo encapsulated within these exosomes, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and proteins, the review uncovers key regulatory mechanisms governing these effects. Noteworthy miRNAs, such as miR-155, miR-196a-5p, and miR-221-3p, are highlighted for their pivotal roles in mediating TAM-derived exosomal communication and influencing downstream targets. Moreover, the review explores the impact of TAM-derived exosomes on the immune microenvironment, particularly their ability to modulate immune cell function and foster immune evasion. The discussion encompasses the regulation of programmed cell death ligand 1 (PD-L1) expression and subsequent impairment of CD8 + T cell activity, unraveling the immunosuppressive effects of TAM-derived exosomes. With an eye toward clinical implications, the review underscores the potential of TAM-derived exosomes as diagnostic markers and therapeutic targets. Their involvement in cancer progression, metastasis, and therapy resistance positions TAM-derived exosomes as key players in reshaping treatment strategies. Finally, the review outlines future directions, proposing avenues for targeted therapies aimed at disrupting TAM-derived exosomal functions and redefining the tumor microenvironment.
    Keywords:  Cancer; Exosome; Extracellular vesicle; Therapeutic approach; Tumor-associated macrophages
    DOI:  https://doi.org/10.1016/j.intimp.2024.112406
  2. Life Sci. 2024 Jun 06. pii: S0024-3205(24)00377-1. [Epub ahead of print] 122787
    Exosomal miR-1228-5p down-regulates DUSP22 to promotes cell proliferation and migration in small cell lung cancer.
    Xiaoqian Mu, Chaonan Yu, Yanqiu Zhao, Xiufeng Hu, He Wang, Yongqiang He, Hongbo Wu.
       BACKGROUND: Exosomes play a crucial role in promoting tumor progression, dissemination, and resistance to treatment. These extracellular vesicles hold promise as valuable indicators for cancer detection. Our investigation focuses on exploring the significance and clinical relevance of exosomal miRNAs in small cell lung cancer (SCLC).
    METHODS: Serum exosomes were isolated from both SCLC patients and healthy controls, and subjected to exosomal miRNA sequencing analysis. Mimics and inhibitors were employed to investigate the function of exosomal miR-1128-5p in cell migration and proliferation, both in vitro and in vivo. Western blot and luciferase assay were utilized to identify the interaction between miR-1228-5p and dual specificity phosphatase 22 (DUSP22).
    RESULTS: Exosomal miRNA sequencing analysis revealed enrichment of specific miRNAs in SCLC compared to healthy controls. Circulating miR-1228-5p was upregulated in SCLC patients, associated with advanced stages, suggesting its potential oncogenic role. In vitro, miR-1228-5p expression was significantly higher in SCLC cells than in normal cells. SCLC cell-derived exosomes contained elevated levels of miR-1228-5p, facilitating its entry into co-cultured cells. Notably, migration and proliferation induced by SCLC exosomes were mainly mediated by miR-1228-5p. In vivo experiments confirmed these findings. Western blot analysis demonstrated miR-1228-5p's regulation of DUSP22 expression, and luciferase reporter assay validated DUSP22 as a direct target gene. Overexpressing DUSP22 counteracted miR-1228-5p's promotion of SCLC cell proliferation and migration.
    CONCLUSIONS: Collectively, our results suggest that exosomes play a role in facilitating cancer growth and metastasis by delivering miR-1228-5p. Moreover, circulating exosomal miR-1228-5p may serve as a potential marker for SCLC diagnosis and prognosis.
    Keywords:  Dual specificity phosphatase 22; Exosomes; Small cell lung cancer; miR-1228-5p
    DOI:  https://doi.org/10.1016/j.lfs.2024.122787
  3. World J Gastroenterol. 2024 May 28. 30(20): 2618-2620
    Exosomal microRNAs in hepatocellular carcinoma, expanding research field.
    Bo-Hao Zheng, Xiao-Jian Ni, Hou-Bao Liu.
      In this editorial we comment on the review by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023. Small extracellular vesicles (exosomes) play important roles in the tumor microenvironment. In this review, the authors introduce the following points: (1) The composition and function of exosomal microRNAs (miRNAs) of different cell origins in hepatocellular carcinoma (HCC); (2) the crosstalk between exosomal miRNAs from stromal cells and immune cells in the tumor microenvironment and the progression of HCC; and (3) the potential applicability of exosomal miRNAs derived from mesen-chymal stem cells in the treatment of HCC. In addition, the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC was introduced. In this review, the authors give us an overview of the exosomal RNA and summarize the function of exosomal RNA in HCC, which provides a deeper understanding of exosomal miRNAs to the readers.
    Keywords:  Exosomes; Hepatocellular carcinoma; Liver cancer; MicroRNA; Tumor microenvironment
    DOI:  https://doi.org/10.3748/wjg.v30.i20.2618
  4. Future Oncol. 2024 May 30. 1-15
    Dysregulation of exosomal miRNAs and their related genes in head and neck cancer patients.
    Muhammad Rizwan, Ishrat Mahjabeen, Nida Sarosh Ashraf, Maryam Arshad, Muhammad Shahbaz Haris, Mahmood Akhtar Kayani.
      Aim: The present study aimed to figure out the potential role of exosomal microRNAs, and their targeted genes in HNC detection/diagnosis. Methods: In the present study, exosomes were extracted from the serum samples of 400 HNC patients and 400 healthy controls. Exosomes were characterized using TEM, NTA, TEM-immunogold labeling and ELISA. Quantitative PCR was used to measure the expression level of exosomal miRNA-19a, miRNA-19b and targeted genes SMAD2 and SMAD4 in HNC patients and controls. Results: The deregulation of miR-19a (p < 0.01), miR-19b (p < 0.03), SMAD2 (p < 0.04) and SMAD4 (p < 0.04) was observed in HNC patients vs controls. Conclusion: ROC curve and Kaplan-Meier analysis showed the good diagnostic/prognostic value of selected exosomal microRNAs and related genes in HNC patients.
    Keywords:  HNC; SMAD2; SMAD4; diagnostic markers; exosomal microRNA; exosomes; miR-17-92 polycistronic cluster; miR-19a; miR-19b; quantitative PCR
    DOI:  https://doi.org/10.1080/14796694.2024.2351355
  5. Transl Oncol. 2024 Jun 08. pii: S1936-5233(24)00135-9. [Epub ahead of print]46 102008
    Exosomal mRNA Cargo are biomarkers of tumor and immune cell populations in pediatric osteosarcoma.
    Jonathan Lian K Ong, Nur Fatimah Farzanah Jalaludin, Meng Kang Wong, Sheng Hui Tan, Clara Angelina, Sarvesh A Sukhatme, Trifanny Yeo, Chwee Teck Lim, York Tien Lee, Shui Yen Soh, Tony K H Lim, Timothy Kwang Yong Tay, Kenneth Tou En Chang, Zhi Xiong Chen, Amos Hp Loh.
      Osteosarcoma is the commonest malignant bone tumor of children and adolescents and is characterized by a high risk of recurrence despite multimodal therapy, especially in metastatic disease. This suggests the presence of clinically undetected cancer cells that persist, leading to cancer recurrence. We sought to evaluate the utility of peripheral blood exosomes as a more sensitive yet minimally invasive blood test that could aid in evaluating treatment response and surveillance for potential disease recurrence. We extracted exosomes from the blood of pediatric osteosarcoma patients at diagnosis (n=7) and after neoadjuvant chemotherapy (n=5 subset), as well as from age-matched cancer-free controls (n=3). We also obtained matched tumor biopsy samples (n=7) from the cases. Exosome isolation was verified by CD9 immunoblot and characterized on electron microscopy. Profiles of 780 cancer-related transcripts were analysed in mRNA from exosomes of osteosarcoma patients at diagnosis and control patients, matched post-chemotherapy samples, and matched primary tumor samples. Peripheral blood exosomes of osteosarcoma patients at diagnosis were significantly smaller than those of controls and overexpressed extracellular matrix protein gene THBS1 and B cell markers MS4A1 and TCL1A. Immunohistochemical staining of corresponding tumor samples verified the expression of THBS1 on tumor cells and osteoid matrix, and its persistence in a treatment-refractory patient, as well as the B cell origin of the latter. These hold potential as liquid biopsy biomarkers of disease burden and host immune response in osteosarcoma. Our findings suggest that exosomes may provide novel and clinically-important insights into the pathophysiology of cancers such as osteosarcoma.
    Keywords:  Exosome; MS4A1; Osteosarcoma; TCL1A; THBS1
    DOI:  https://doi.org/10.1016/j.tranon.2024.102008
  6. Blood Adv. 2024 Jun 13. pii: bloodadvances.2023012464. [Epub ahead of print]
    Anti-BCMA-engineered Exosomes for Bortezomib Targeted Delivery in Multiple Myeloma.
    Shushu Yuan, Qi Li, Chuan He, Mengli Bing, Xinyun Zhang, Hao Xu, Zhiming Wang, Meifang Zhao, Yuchen Zhang, Yali Chai, Bingzong Li, Wenzhuo Zhuang.
      Exosomes have emerged as promising vehicles for delivering therapeutic cargoes to specific cells or tissues, owing to their superior biocompatibility, reduced immunogenicity, and enhanced targeting capabilities compared to conventional drug delivery systems. In this study, we developed a delivery platform utilizing exosomes derived from monocytes, specifically designed for targeted delivery of Bortezomib (Btz) to multiple myeloma (MM) cells. Our approach involved the genetic modification of monocytes to express antibodies targeting B cell maturation antigen (anti-BCMA), as BCMA selectively expresses on myeloma cells. This modified anti-BCMA was then efficiently incorporated into the monocyte-derived exosomes. These adapted exosomes effectively encapsulated Bortezomib, leading to enhanced drug accessibility within MM cells and sustained intracellular accumulation over an extended period. Remarkably, our results demonstrated that anti-BCMA-Exo-Btz outperformed free Btz in vitro, exhibiting a more potent myeloma-suppressive effect. In orthotopic MM xenograft models, anti-BCMA-Exo-Btz exhibited a significant anti-tumor effect compared to free Btz. Furthermore, it demonstrated remarkable specificity in targeting Bortezomib to myeloma cells in vivo. Importantly, we observed no significant histological damage in mice treated with anti-BCMA-Exo-Btz and a slight effect on PBMCs. Additionally, our study highlighted the multifunctional potential of monocyte-exosomes, which induced cell apoptosis, mediated immune responses, and enhanced the osteogenic potential of mesenchymal stromal cells. In conclusion, our study suggests that exosomes modified with targeting ligands hold therapeutic promise for delivering Bortezomib to myelomas, offering substantial potential for clinical applications.
    DOI:  https://doi.org/10.1182/bloodadvances.2023012464
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