bims-exocan 2025-10-05 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2025–10–05
seven papers selected by
Muhammad Rizwan, COMSATS University

Exosomal FGG promotes colorectal cancer liver metastases through inducing angiogenic pre-metastatic niche formation.
Exosomal transfer of miR-223-3p from carcinoma-associated fibroblasts promotes the malignant properties and chemoresistance of colon cancer cells by targeting NF2/Hippo signaling.
MDA-9/Syntenin promotes glioma cell proliferation and invasion via exosome-mediated activation of the PI3K-AKT signaling pathway.
Engineered exosomes: a promising approach for overcoming challenges in pancreatic cancer therapy.
TGF-β-Enriched Exosomes from Acute Myeloid Leukemia Activate Smad2/3-MMP2 and ERK1/2 Signaling to Promote Leukemic Cell Proliferation, Migration, and Immune Modulation.
Extracellular-vesicle-mediated NLRP3 signaling in cancer.
Unlocking the therapeutic potential of tumor-derived small extracellular vesicles in cancer immunotherapy: A multifaceted approach.

Arch Biochem Biophys. 2025 Sep 25. pii: S0003-9861(25)00339-X. [Epub ahead of print]774 110625

Exosomal FGG promotes colorectal cancer liver metastases through inducing angiogenic pre-metastatic niche formation.

Lingling Yang, Lifang Chen, Xin Chen, Haiqiang Huang, Hui Zhu, Liangtao Zeng, Jun Huang, Hao Ding.

  Angiogenesis is a defining feature of a pre-metastatic niche and is essential for primary colorectal cancer (CRC) tumor metastasis. Epithelial-mesenchymal transition (EMT) also serves as a critical driver of CRC tumor metastatic progression. Here, we hypothesized that exosomes from CRC cells promoted liver metastasis by remodeling tumor microenvironment. To verify this hypothesis, exosomes from CRC cells were isolated and identified, and the effects of these exosomes on human umbilical vein endothelial cells (HUVECs) were investigated. Exosomes from CRC cells promoted vascularization, permeability and migration of HUVECs. Mechanistically, exosomes derived from CRC cells delivered Fibrinogen gamma (FGG) to exert their effects on HUVECs. Furthermore, FGG downregulated the levels of VE-cadherin and E-cadherin in CRC cells, while upregulating N-cadherin and vimentin levels, thereby enhancing endothelial permeability and promoting EMT. In vivo experiments demonstrated that FGG downregulated VE-cadherin in CRC tissues and upregulated CD31 in liver tissues, ultimately leading to an increased number of metastatic liver nodules in a mouse model of CRC liver metastasis. In conclusion, FGG facilitates CRC liver metastasis by regulating key angiogenic, adhesion and mesenchymal markers via exosome-mediated mechanisms, resulting enhanced angiogenesis, vascular permeability, and EMT induction. These findings offer new insights into the mechanisms and treatment strategies of CRC liver metastasis.

Keywords:  Colorectal cancer; Fibrinogen gamma; Liver metastasis; Pre-metastatic niche; VE-Cadherin

DOI:  https://doi.org/10.1016/j.abb.2025.110625
Med Oncol. 2025 Sep 30. 42(11): 503

Exosomal transfer of miR-223-3p from carcinoma-associated fibroblasts promotes the malignant properties and chemoresistance of colon cancer cells by targeting NF2/Hippo signaling.

Jiaqi Zhao, Jiarui Zhang, Jing Liu, Likun Zan.

  Cancer-associated fibroblasts (CAFs) play a key role in malignant progression and chemoresistance of cancer. Accumulating studies indicate that exosomal transfer of microRNAs from CAFs to cancer cells is responsible for the effects of CAFs in cancer (Wang et al. in Cancers, 2021, https://doi.org/10.3390/cancers13133160 ). In the present study, we explored the impact of CAFs-derived exosomes on tumorigenesis and chemoresistance of colon cancer, and potential microRNAs involved in this process. CAFs were isolated form colon cancer samples. CAFs-derived exosomes were separated by ultracentrifugation. Differentially expressed microRNAs were identified by microRNA expression array. The function of CAFs-derived exsomes and exosomal microRNAs were evaluated by cell viability assay, soft agar assay, transwell invasion assay, sphere formation assay, qRT-PCR, tumor xenograft model, flow cytometry, western blot, luciferase reporter assay, biotin microRNA pull-down assay. In our study, CAFs-derived exosomes promoted proliferation, anchorage-independent growth, invasion, stemness, tumor xenograft growth and 5-FU resistance of colon cancer cells. MiR-223-3p was significantly upregulated in CAFs-derived exosomes and serum or tissue samples of colon cancer patients. Exosomal transfer of miR-223-3p facilitated malignant properties and 5-FU resistance of colon cancer cells. Moreover, NF2 was identified as a downstream target for miR-223-3p. Restored NF2 expression partially abrogated the effects caused by exosomal transfer of miR-223-3p in colon cancer cells. In addition, exosomal miR-223-3 regulated Hippo pathway in colon cancer cells by targeting NF2. Our results indicated that exosomal transfer of miR-223-3p from CAFs to colon cancer cells promoted malignant properties and chemoresistance through NF2/Hippo pathway.

Keywords:  Associated fibroblasts (CAFs); Cancer; Colon cancer; Exosomal miR-223-3p; Neurofibromatosis type 2 (NF2)

DOI:  https://doi.org/10.1007/s12032-025-03063-y
Biochem Biophys Res Commun. 2025 Sep 26. pii: S0006-291X(25)01436-6. [Epub ahead of print]786 152720

MDA-9/Syntenin promotes glioma cell proliferation and invasion via exosome-mediated activation of the PI3K-AKT signaling pathway.

Yanwen Zheng, Xiaoting Yu, Zhaomin Zhong, Ming Li.

  Exosomes, lipid bilayer-enclosed extracellular vesicles, transfer bioactive molecules to mediate intercellular communication and tumour progression. Melanoma differentiation-associated gene 9 (MDA-9/Syntenin) regulates exosome biogenesis, but its role in glioma-derived exosomes remains poorly understood, with prior studies focusing primarily on MDA-9's intracellular functions in glioma cells. Here, we investigate MDA-9-mediated exosomal contributions to glioma pathogenesis. We found that MDA-9 is upregulated in glioma tissues, correlating with poor prognosis in glioma patients. Exosomes from MDA-9-overexpressing glioma cells significantly enhanced recipient glioma cell proliferation and invasion compared to controls. Mechanistically, these exosomes activated the PI3K-AKT pathway, upregulating MMP9 and c-MYC to drive cell proliferation and invasion. These findings reveal a novel role of the exosomal MDA-9-PI3K-AKT-MMP9/c-MYC axis in glioma progression, highlighting MDA-9 as a promising therapeutic target.

Keywords:  AKT; Cell invasion; Cell proliferation; Exosomes; Glioma; MDA-9

DOI:  https://doi.org/10.1016/j.bbrc.2025.152720
J Nanobiotechnology. 2025 Sep 29. 23(1): 619

Engineered exosomes: a promising approach for overcoming challenges in pancreatic cancer therapy.

Mo Sha, Yang Gao, Xu Yin, Xueyao Li, Caiqi Liu, Shuang Li.

  Pancreatic cancer (PC) is among the deadliest types of cancer, with very low chances of survival. It is often asymptomatic in the early stage, making diagnosis difficult. Therefore, it is typically found at an advanced stage, resulting in patients missing the opportunity for radical surgery. The complex biological characteristics of PC, coupled with the difficulties in drug delivery and tumor resistance, limit the effectiveness of drug therapy. Due to their compatibility with biological systems and low likelihood of triggering an immune response, exosomes are seen as a promising method for drug delivery. They are capable of targeting and penetrating tissues inside the body and can be engineered through surface modification and drug loading. Engineered exosomes possess controllable and diverse drug-carrying capabilities, which can enhance drug internalization and cellular uptake. Owing to their special properties and the potential to overcome the drawbacks of standard therapies, engineered exosomes have appeared as a promising treatment option. This review aims to comprehensively summarize the current application status and progress of engineered exosomes used in PC therapy.

Keywords:  Cancer therapy; Delivery system; Engineered exosomes; Pancreatic cancer

DOI:  https://doi.org/10.1186/s12951-025-03697-0
Curr Issues Mol Biol. 2025 Aug 27. pii: 690. [Epub ahead of print]47(9):

TGF-β-Enriched Exosomes from Acute Myeloid Leukemia Activate Smad2/3-MMP2 and ERK1/2 Signaling to Promote Leukemic Cell Proliferation, Migration, and Immune Modulation.

Jie Jia.

  Exosomes are extracellular vesicles secreted by all cell types, transporting nucleic acids, proteins, lipids, and metabolites. They are known to influence tumor biology by modulating cellular proliferation, invasion, and apoptosis. In acute myeloid leukemia (AML), the precise functions of exosomes remain incompletely characterized. Here, we present an integrated multi-omics study combining single-cell RNA sequencing (scRNA-seq) of bone marrow aspirates from AML patients and healthy donors with transcriptomic profiling of purified exosomes. This approach uniquely allowed us to link cellular transcriptional states with exosome content and function. We discovered a significant upregulation of exosome-related transcriptional activity in AML cells. Purified AML exosomes showed enhanced translational, transcriptional, and metabolic activity compared to those from healthy donors. Notably, these exosomes were highly enriched in transforming growth factor-β (TGF-β), a key regulator of tumor progression. Functional assays confirmed that AML-derived exosomes promote leukemic cell proliferation and migration. Mechanistically, these effects are mediated via activation of the Smad2/3-MMP2 and ERK1/2 signaling pathways. Furthermore, cell-cell interaction analysis revealed that AML exosomes reshape the bone marrow immune microenvironment by upregulating multiple immunoregulatory genes and pathways, revealing a novel immunomodulatory role. This study provides the first integrative demonstration that TGF-β-enriched exosomes actively drive AML progression through combined enhancement of leukemic aggressiveness and immune microenvironment remodeling. Our findings highlight exosomes and their signaling cascades as promising therapeutic targets, offering new avenues for innovative AML treatments.

Keywords:  AML; TGF-β; exosomes; immune modulation; migration; proliferation

DOI:  https://doi.org/10.3390/cimb47090690
Exp Cell Res. 2025 Sep 29. pii: S0014-4827(25)00378-7. [Epub ahead of print]452(2): 114778

Extracellular-vesicle-mediated NLRP3 signaling in cancer.

Harish C Chandramoorthy, Raed Obaid Saleh, Viralkumar Mandaliya, Roopashree R, Hanen Mahmod Hulail, Subasini Uthirapathy, Renu Arya, Deepak Nathiya, Dina M R AlKhafaf.

  The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome has recently been characterized as a major player in cancer-related inflammation, tumor progression, immune modulation, and metastasis. The role of extracellular vesicles (EVs), such as exosomes and microvesicles, as active carriers of NLRP3 signaling components is increasingly being recognized, as they modulate the tumor microenvironment as well as distant tissues primed for metastasis. This study will address the diverse roles of EV-mediated NLRP3 signaling in cancer immunopathogenesis, with a particular emphasis on its role in establishing a pre-metastatic niche and immune evasion. Tumor-derived EVs that include NLRP3 as cargo can reprogram stroma and immune cells at secondary sites in the body to support a metabolic role associated with metastatic colonization. While tumor-derived EVs promote extracellular matrix remodeling, angiogenesis, and the recruitment of immune-suppressive cells, this cascade of processes permits the development of a permissive niche for metastatic colonization, and simultaneously impairs anti-tumor immune surveillance. The provided EV-mediated crosstalk also enables tumor cells to evade immune detection through the downregulation of antigen-presenting cells and the activation of immune-suppressive pathways via NLRP3-dependent mechanisms. The molecular mechanisms underlying EV-driven inflammasome signaling could pave the way for the identification of a novel and specific biomarker, in which its modulation could potentially affect the immune system in the tumor microenvironment (TME) and participate in cancer immunopathogenesis. This review highlights the need to dissect further the interactions and context-specific roles of EV-NLRP3 across cancers to identify new therapeutic strategies for preventing metastasis and enhancing immune therapies.

Keywords:  Extracellular vesicles; Immune evasion; Inflammation mediators; NLRP3 inflammasome; Neoplasm metastasis; Tumor microenvironment

DOI:  https://doi.org/10.1016/j.yexcr.2025.114778
Biomaterials. 2025 Sep 22. pii: S0142-9612(25)00652-0. [Epub ahead of print]327 123733

Unlocking the therapeutic potential of tumor-derived small extracellular vesicles in cancer immunotherapy: A multifaceted approach.

Hyewon Ko, Chan Ho Kim, Soyoung Son, Jung Min Shin, Jae Hyung Park.

  Cancer immunotherapy represents a remarkable breakthrough in oncology. However, the efficacy of existing therapeutic modalities is observed in only a subset of patients, highlighting the need for further advancements. Tumor-derived small extracellular vesicles (T-sEVs), nano-sized extracellular vesicles secreted by cancer cells, have been the focus of significant interest as contributors to immunotherapy resistance. T-sEVs serve as biomarkers and therapeutic targets owing to their roles in mediating intercellular communication, promoting tumor progression and metastasis, and fostering immunosuppressive microenvironments that hinder immunotherapy. However, when appropriately utilized and their unique properties leveraged, T-sEVs exhibit therapeutic potential. This review explores the potential of T-sEVs as a multifaceted therapeutic option for enhancing cancer immunotherapies. It overviews the emerging research trends and applications of three main therapeutic strategies: eliminating immunosuppressive T-sEVs, utilizing T-EVs as drug carriers with tumor-targeting capabilities, and exploiting T-EVs as antigenic platforms to enhance anticancer immunity. In conclusion, the review provides insights into the potential clinical applications of T-sEV-based therapies and discusses future directions for their development.

Keywords:  Cancer immunotherapy; Cancer vaccine; Drug delivery; Exosome inhibition; Tumor microenvironment; Tumor-derived small extracellular vesicles

DOI:  https://doi.org/10.1016/j.biomaterials.2025.123733