bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2025–11–23
six papers selected by
Muhammad Rizwan, COMSATS University
  1. Exosomal FOSL1 From Cancer-associated Fibroblasts Drives the Progression and Pro-tumorigenic M2 Macrophage Polarization of Hepatocellular Carcinoma By Activating PLAU Transcription.
  2. Extracellular vesicles as biomarkers in cancer diagnosis and prognosis.
  3. Exosomal transfer of miR-124 from engineered NK-92 cells inhibits breast cancer cell migration and induces apoptosis.
  4. Identification and prognostic prediction of high-risk multiple myeloma by exosomal microRNA.
  5. Bioengineered Extracellular Vesicles in Emerging Cancer Vaccine Platforms.
  6. Exosomal Pparα derived from cancer cells induces CD8+ T cell exhaustion in hepatocellular carcinoma through the miR-27b-3p/TOX axis.
  1. Appl Biochem Biotechnol. 2025 Nov 20.
    Exosomal FOSL1 From Cancer-associated Fibroblasts Drives the Progression and Pro-tumorigenic M2 Macrophage Polarization of Hepatocellular Carcinoma By Activating PLAU Transcription.
    Kai Bai, Ruopeng Liang, Jian Li, Kun Zhao.
      Exosomes derived from cancer-associated fibroblasts (CAFs) play a crucial role in cancer development. Fos-like antigen 1 (FOSL1) exhibits oncogenic properties across various malignancies. However, the specific role of FOSL1 in CAFs-derived exosomes (CAFs-EXO) in hepatocellular carcinoma (HCC) has not been previously explored. This study aimed to investigate whether CAFs-EXO transfer FOSL1 to HCC cells and to examine the functional consequences of this transfer. HCC-related CAFs and their exosomes were used to incubate HCC cells. Cell proliferation and migration/invasion were assessed. The percentage of CD11b+CD206+ macrophages was measured. The FOSL1/PLAU relationship was validated by chromatin immunoprecipitation (ChIP) and luciferase assays. FOSL1 expression was increased in CAFs-EXO compared with normal controls (3.36 ± 0.25 vs. 1.00 ± 0.04, P < 0.001). CAFs-EXO transmitted FOSL1 into HCC cells, promoting HCC cell proliferation (Huh-7 cells: 63.93 ± 2.68 vs. 54.37 ± 0.8, P < 0.01; Hep3B: 63.27 ± 5.13 vs. 51.9 ± 1.75, P < 0.01). CAFs-EXO enhanced cell migration (Huh-7 cells: 197.33 ± 12.06 vs. 153.0 ± 6.25, P < 0.05; Hep3B: 215.33 ± 29.14 vs. 143.0 ± 7.55, P < 0.01) and invasion (Huh-7 cells: 176.67 ± 19.86 vs. 130.33 ± 8.62, P < 0.01; Hep3B: 191.0 ± 8.19 vs. 121.0 ± 7.0, P < 0.001). CAFs-EXO increased pro-tumorigenic M2 macrophage polarization by transmitting FOSL1. Moreover, CAFs-EXO affected the in vivo growth and metastasis of HCC cells through FOSL1. Mechanistically, FOSL1 activated PLAU transcription. FOSL1 promoted HCC cell malignant phenotypes and pro-tumorigenic M2 macrophage polarization by upregulating PLAU. Additionally, PLAU depletion suppressed HCC malignant phenotypes and decreased pro-tumorigenic M2 macrophage polarization. This study provides the first evidence that CAFs-EXO transport FOSL1 into HCC cells, thereby influencing HCC progression through the activation of PLAU transcription. These findings highlight the FOSL1/PLAU axis as a previously unrecognized therapeutic target in HCC.
    Keywords:  Cancer-associated fibroblasts; Exosomes; FOSL1; Hepatocellular carcinoma; Tumor-associated macrophages
    DOI:  https://doi.org/10.1007/s12010-025-05404-z
  2. Curr Top Membr. 2025 ;pii: S1063-5823(25)00012-2. [Epub ahead of print]96 317-354
    Extracellular vesicles as biomarkers in cancer diagnosis and prognosis.
    Marina Malheiros Araújo Silvestrini, Fábio Magalhães-Gama, Andréa Teixeira-Carvalho.
      Extracellular vesicles (EVs) have emerged as key mediators in cancer biology, playing critical roles in intercellular communication within the tumor microenvironment. These nano-sized particles carry diverse molecular cargos, including proteins, lipids, DNA, and various RNA species, which reflect the biological state of their cells of origin. This chapter provides a comprehensive overview of the diagnostic and prognostic potential of EVs across a wide spectrum of tumor types, following the World Health Organization (WHO) tumor classification. We discuss the contribution of EVs in genetic tumor syndromes, solid tumors (such as skin, breast, digestive, and thoracic cancers), hematolymphoid malignancies, and pediatric cancers. Special emphasis is placed on the utility of EVs in liquid biopsy applications, offering minimally invasive alternatives for early diagnosis, monitoring of disease progression, treatment response, and detection of relapse. Furthermore, the chapter highlights specific EV-associated biomarkers, including proteins, microRNAs, long non-coding RNAs, and circular RNAs, identified in various biofluids such as blood, urine, saliva, and cerebrospinal fluid. Despite the promising potential of EVs as clinical tools, several challenges remain, including standardization of isolation and characterization methods, biological heterogeneity of EV populations, and the need for large-scale validation studies. Addressing these hurdles will be critical for the successful translation of EV-based biomarkers into routine oncology practice.
    Keywords:  Biomarkers; Cancer; Exosomes; Extracellular vesicles; Liquid biopsy; Microvesicles; Tumor microenvironment
    DOI:  https://doi.org/10.1016/bs.ctm.2025.07.002
  3. Med Oncol. 2025 Nov 18. 43(1): 6
    Exosomal transfer of miR-124 from engineered NK-92 cells inhibits breast cancer cell migration and induces apoptosis.
    Amirabbas Salmani, Amir Atashi, Mina Soufi Zomorrod, Mohammad Kamalabadi-Farahani, Asieh Heirani-Tabasi, Masoud Soleimani.
      This study aimed to investigate the feasibility of using engineered NK-92 cell-derived exosomes to deliver miR-124 to breast cancer cell lines and to assess the anti-tumor effects of these exosomes in breast cancer cell lines. In this study, the NK-92 cell line was genetically engineered to overexpress miR-124. Subsequently, exosomes were isolated from the modified cell line. The effects of these NK-92-miR-124 exosomes were assessed on the proliferation, apoptosis, and migration of three different subtypes of breast cancer cell lines (MCF-7, MDA-MB-231, and SK-BR-3) using MTT assays, Annexin V/PI staining, and scratch tests, respectively. Finally, the results from all experiments were compared with the outcomes obtained from the treatment of breast cancer cell lines with NK-92 exosomes. All comparisons were made under the same experimental conditions. Our findings demonstrated that miR-124 was effectively delivered to breast cancer cell lines via engineered NK-92-derived exosomes. Furthermore, these NK-92-miR-124-loaded exosomes exhibited notable anti-tumor effects, such as reducing cell proliferation and migration across all three breast cancer cell lines. Additionally, they significantly enhanced apoptosis in MCF-7 and MDA-MB-231 breast cancer cell lines compared to NK-92-derived exosomes. Our study demonstrated that engineered NK-92-derived exosomes can effectively deliver miR-124 to breast cancer cells, leading to reduced migration and enhanced apoptosis. However, the anti-tumor effects varied among different breast cancer cell lines.
    Keywords:  Breast cancer; Exosome; MiR-124; NK-92
    DOI:  https://doi.org/10.1007/s12032-025-03107-3
  4. Front Oncol. 2025 ;15 1659708
    Identification and prognostic prediction of high-risk multiple myeloma by exosomal microRNA.
    Ying Tian, Wenjiao Tang, Chunlan Zhang, Juan Xu, Yunfan Yang, Qinyu Liu, Xushu Zhong, Jie Wang, Caigang Xu.
       Introduction: Circulating exosomal miRNAs have emerged as important tools for liquid biopsy in cancer diagnosis and prognosis prediction. This project establishes a plasma exosomal miRNA-based system for diagnosing multiple myeloma(MM) and evaluating patient prognosis, aiming to provide novel strategies for diagnosis and early warning in high-risk MM patients.
    Methods: The study prospectively collected plasma samples and clinical data of newly diagnosed multiple myeloma (NDMM) patients and healthy controls (HCs). Plasma samples were obtained in MM patients before the administration of any chemotherapy. The study comprises three stages to identify plasma exosomal miRNAs associated with the diagnosis and prognosis of MM. In the screening stage, next-generation sequencing of plasma circulating exosomes was performed in 17 NDMM patients and 8 HCs to screen the candidate differentially expressed miRNAs. We further investigated a testing stage of 80 individuals (including 60 NDMM patients and 20 HCs) and a verification stage of 130 NDMM through qPT-PCR.
    Results: Utilizing a testing cohort of 60 newly diagnosed MM cases, we developed a diagnostic model based on six miRNAs (hsa-miR-192-5p, hsa-miR-10a-5p, hsa-miR-10b-3p, hsa-miR-148a-3p, hsa-miR-193b-5p, hsa-miR-483-3p) achieving an AUC of 0.94, sensitivity of 0.88, and specificity of 0.94. In a validation cohort of 130 MM patients, we developed a prognostic nomogram that amalgamated the expression levels of three key exosomal miRNAs (hsa-miR-193b-5p, miR-483-3p, and let-7b-5p) with critical clinical variables, which exhibits superior performance compared to the ISS staging system. This integrative model effectively predicted 1-, 3-, and 5-year survival probabilities, thereby stratifying patients into distinct risk categories for enhanced clinical decision-making and personalized follow-up strategies.
    Discussion: This research validates the diagnostic and prognostic utility of exosomal miRNA models in MM, emphasizing their discriminative and predictive capabilities.
    Keywords:  diagnostic; exosomal miRNA; liquid biopsy; multiple myeloma; prognostic
    DOI:  https://doi.org/10.3389/fonc.2025.1659708
  5. Small Sci. 2025 Nov;5(11): 2500270
    Bioengineered Extracellular Vesicles in Emerging Cancer Vaccine Platforms.
    Wonkyung Ahn, Yeram Lee, Gi-Hoon Nam, Jae Bem You, Eun Jung Lee.
      Amid the evolving landscape of immunotherapy, the pursuit of safer, more precise, and broadly applicable vaccine platforms has intensified. While conventional technologies-such as lipid nanoparticle-based mRNA systems-achieved unprecedented success in infectious disease prophylaxis, their limitations in safety and durability have prompted the search for alternatives to address more complex immunological challenges, particularly in oncology. Within this context, extracellular vesicle (EV)-based vaccines have emerged as a next-generation platform. These endogenously derived nanoscale vesicles, secreted by nearly all cell types, mirror the immunological identity of their origin and support diverse immune functions. Advances in EV research have enabled modular vaccine design through strategies such as antigen loading, surface engineering, and cytokine-driven modulation. Depending on their cellular source-dendritic cells, macrophages, lymphocytes, or tumor cells-EVs exhibit distinct immunological properties that allow tailored engagement of immune responses. Rather than acting solely as delivery vehicles, they integrate antigen transport, immune activation, and adjuvant effects within a single structure. Recent progress in EV-based cancer vaccine development is reviewed, encompassing vesicle biogenesis, engineering strategies, and delivery optimization, alongside emerging preclinical and clinical evidence supporting their translational potential. Finally, key challenges, including vesicle heterogeneity and manufacturing standardization, are outlined as factors that must be addressed to enable clinical advancement.
    Keywords:  cancer immunotherapies; cancer vaccines; dendritic cell‐derived extracellular vesicles; exosomes; extracellular vesicles; tumor‐derived extracellular vesicles; vaccines
    DOI:  https://doi.org/10.1002/smsc.202500270
  6. Chin Med J (Engl). 2025 Nov 17.
    Exosomal Pparα derived from cancer cells induces CD8+ T cell exhaustion in hepatocellular carcinoma through the miR-27b-3p/TOX axis.
    Wenjun Zhong, Nianan Luo, Yafeng Chen, Jiangbin Li, Zhujun Yang, Rui Dong.
       BACKGROUND: Cluster of differentiation 8 positive (CD8+) T cells play a crucial role in the response against tumors, including hepatocellular carcinoma (HCC), where their dysfunction is commonly observed. While the association between elevated peroxisome proliferator-activated receptor alpha (PPARα) expression in HCC cells and exosomes and unfavorable prognosis in HCC patients is well-established, the underlying biological mechanisms by which PPARα induces CD8+ T cell exhaustion mediated by HCC exosomes remain poorly understood.
    METHODS: Bioinformatics analyses and dual-luciferase reporter assays were used to investigate the regulation of microRNA-27b-3p (miR-27b-3p) and thymocyte selection-associated high mobility group box (Tox) by Pparα. In vitro and in vivo experiments were conducted to validate the effects of HCC-derived exosomes, miR-27b-3p overexpression, and Pparα on T cell function. Exosome characterization was confirmed using transmission electron microscopy, Western blotting, and particle size analysis. Exosome tracing was performed using small animal in vivo imaging and confocal microscopy. The expression levels of miR-27b-3p, Pparα, and T cell exhaustion-related molecules (Tox, Havcr2, Pdcd1) were detected using qRT-PCR analysis, Western blotting analysis, immunofluorescence staining, and flow cytometry analysis.
    RESULTS: Pparα expression was significantly increased in HCC and negatively correlated with prognosis. It showed a positive correlation with Tox and a negative correlation with miR-27b-3p. The overexpressed Pparα from HCC cells was delivered to CD8+ T cells via exosomes, which absorbed miR-27b-3p both in vitro and in vivo, acting as "miRNA sponges". Further experiments demonstrated that Pparα can inhibit the negative regulation of Tox mediated by miR-27b-3p through binding to its 3'untranslated regions.
    CONCLUSIONS: HCC-derived exosomes deliver Pparα to T cells and promote CD8+ T cell exhaustion and malignant progression of HCC via the miR-27b-3p/TOX regulatory axis. The mechanisms underlying T-cell exhaustion in HCC can be utilized for the advancement of anticancer therapies.
    Keywords:  ; Hepatocellular carcinoma; Peroxisome proliferator-activated receptor alpha; Thymocyte selection-associated high mobility group box
    DOI:  https://doi.org/10.1097/CM9.0000000000003894
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