bims-exocan 2025-11-30 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2025–11–30
ten papers selected by
Muhammad Rizwan, COMSATS University

Exosome-Mediated Crosstalk Between Cancer Cells and Tumor Microenvironment.
Extracellular vesicles in cancer: biogenesis, oncogenic mechanisms, biomarker potential, and therapeutic applications.
Exosomal microRNAs as prostate cancer biomarkers and treatments: recent progress.
Exosomal LRG1 derived from highly metastatic non-small cell lung cancer cells accelerates growth, metastasis, and angiogenesis by transcriptional factor NFKB1-mediated SHH upregulation.
[The role of exosomal miRNA in the progression of oral squamous cell carcinoma and its molecular mechanism].
Comparison of the therapeutic potential of exosomes derived from different cells for the treatment of prostate cancer.
Exercise-induced modulation of circulating and exosomal microRNAs and long non-coding RNAs: Molecular signatures in cancer diagnosis, prevention and therapy.
Tumor-derived extracellular vesicles: Bridging communication and next-generation theranostics.
Exosomes derived from ovarian cancer promote the progression of ovarian cancer through macrophage M2 polarization mediated by the THBS1/TGFBI signaling axis.
Plasma-derived exosomal tRF-3004a as a diagnostic biomarker for colorectal cancer.

Cells. 2025 Nov 08. pii: 1750. [Epub ahead of print]14(22):

Exosome-Mediated Crosstalk Between Cancer Cells and Tumor Microenvironment.

Sara H Saad, Alex Kashanchi, Mohammad Asad Zadeh, Anastasia Williams, Elena V Batrakova.

  Exosomes are extracellular vesicles that play a central role in mediating intercellular communication within the tumor microenvironment (TME). Cancer-derived exosomes carry proteins, nucleic acids, and lipids that reshape the phenotype and function of surrounding stromal and immune cells, thereby promoting tumor progression, angiogenesis, metastasis, and resistance to therapy. At the same time, exosomes derived from TME components, including macrophages, dendritic cells, B cells, T cells, fibroblasts, neutrophils, and NK cells, reciprocally influence tumor growth and immune evasion. These bidirectional interactions highlight exosomes as both drivers of tumor progression and regulators of antitumor immunity. In this review, we synthesize current evidence on the diverse mechanisms by which exosomes reprogram immune and stromal cells, with a focus on their dual roles in cancer biology. We also discuss emerging therapeutic strategies to inhibit exosome biogenesis, release, and function, underscoring their translational potential as novel targets for cancer diagnosis and treatment.

Keywords:  B cells; cancer progression; dendritic cells; exosomes; extracellular vesicles (EVs); immune modulation; tumor microenvironment (TME); tumor-associated macrophages (TAMs)

DOI:  https://doi.org/10.3390/cells14221750
Med Oncol. 2025 Nov 25. 43(1): 23

Extracellular vesicles in cancer: biogenesis, oncogenic mechanisms, biomarker potential, and therapeutic applications.

Aditi, Aarush Khajuria, Garima, Gurpreet Kaur, Sachin Kumar Singh, Meenakshi Dhanawat, Neeraj Mittal.

  Extracellular vesicles (EVs) have a significant impact on the process of intercellular communication as well as they also help in the transport of a broad variety of molecules, like lipids, proteins, and nucleic acids, across single to different cells. They contribute to cancer progression by transferring oncogenic proteins, microRNAs, and signaling molecules that promote uncontrolled proliferation, angiogenesis, and suppression of anti-tumor immunity. There is a significant amount of interest among researchers in exosomes, which are a kind of EVs. Exosomes are extremely promising as drug-delivery vehicles, especially in cancer treatment, because they are naturally compatible with living systems, structurally stable, and able to target specific cells. The phospholipid bilayer membrane enables drugs to be delivered to specific cells, allowing therapeutic molecules to reach those cells more easily. Using EVs to deliver drugs is a new idea that might completely change how cancer is treated. Exosome biogenesis, origins, isolation, association with cancer, exosome-related cancer biomarkers, exosome-based biomolecule delivery, advancements, and limits of exosome-based drug delivery systems are regarded as main topics via this review. Furthermore, it is anticipated that the exosome-based understanding of cancer will alter future diagnostic and treatment strategies.

Keywords:  Biomarker; Cancer; Exosomes; Extracellular vesicles; MicroRNAs; Oncogenic communication

DOI:  https://doi.org/10.1007/s12032-025-03145-x
Med Oncol. 2025 Nov 24. 43(1): 16

Exosomal microRNAs as prostate cancer biomarkers and treatments: recent progress.

Maryam Mahjoubin-Tehran, Samaneh Rezaei.

  Prostate cancer is a significant global health concern and the second leading cause of death among males. It is known to affect nearby stromal cells. Exosomes assist these stromal cells in supporting cancer growth and spread. They also contribute to the initiation and dissemination of cancer, as well as to the development of drug-resistant cancer cells. The recent discovery of microRNAs (miRNAs) has drawn attention from cancer researchers due to their role in regulating gene expression. Circulating exosomes may carry extracellular miRNAs that serve as prognostic indicators for cancer. There is an urgent need for new biomarkers to improve prostate cancer diagnosis. Recent studies suggest that serum exosomal miRNAs could be effective, noninvasive biomarkers for specific conditions. Exosomal miRNA has emerged as a reliable biomarker for diagnosing and treating prostate cancer. It may also serve as a potential therapy for the disease. Based on clinical and preclinical research, this review explores current knowledge about exosomal miRNAs in prostate cancer diagnosis and treatment, as well as their potential for disease monitoring. Furthermore, this analysis emphasizes the complex role of exosomal microRNAs in prostate cancer development and treatment resistance, including their impact on immune evasion, stromal cell activation, niche formation, and metabolic alterations.

Keywords:  Biomarker; Exosome; MiRNA; Prostate cancer; Therapeutics

DOI:  https://doi.org/10.1007/s12032-025-03146-w
Cell Signal. 2025 Nov 25. pii: S0898-6568(25)00691-6. [Epub ahead of print]138 112276

Exosomal LRG1 derived from highly metastatic non-small cell lung cancer cells accelerates growth, metastasis, and angiogenesis by transcriptional factor NFKB1-mediated SHH upregulation.

Hao Wu, Chao Zeng, Guodong Wu, Fuyuan Fang, Chunyang Xiao, Liang Li, Yisheng Luo, Chaochao Zhou, Youhui Qian.

  Neovascularization, a critical interstitial component, facilitates rapid tumor cell proliferation, metastasis, and recurrence. Communication between tumor-derived exosomes and endothelial cells promotes tumor progression and angiogenesis. Leucine-rich α2 glycoprotein-1 (LRG1) is abundant in exosomes released by non-small cell lung cancer (NSCLC) tissues and cells. However, the molecular mechanisms underlying exosomal LRG1's regulation of angiogenesis in NSCLC remain unclear. In this study, our study demonstrated that exosomes derived from NSCLC cells with high metastatic potential (HM) could enhance growth, metastasis, and angiogenesis. LRG1 was abundant in these HM NSCLC cell-released exosomes and could be transferred to endothelial cells via exosomes. Exosomal LRG1 stimulated the proliferation, migration, invasion, and tube-forming capacity of endothelial cells in vitro, as well as promoted angiogenesis, tumor growth, and metastasis in vivo. Mechanistic investigations revealed that exosomal LRG1 upregulated Sonic Hedgehog (SHH) by binding to Nuclear Factor-κB subunit 1 (NFKB1) within the SHH promoter. Furthermore, the knockdown of SHH could reverse the proliferation, migration, invasion, and angiogenesis of endothelial cells induced by exosomal LRG1. In conclusion, our study findings reveal that exosomal LRG1 accelerates the progression of NSCLC by NFKB1-induced SHH upregulation, offering a novel research perspective for the diagnosis and treatment of this patient population.

Keywords:  Angiogenesis; Exosomes; LRG1; Non-small cell lung cancer; SHH

DOI:  https://doi.org/10.1016/j.cellsig.2025.112276
Zhonghua Kou Qiang Yi Xue Za Zhi. 2025 Nov 28. 60(12): 1428-1435

[The role of exosomal miRNA in the progression of oral squamous cell carcinoma and its molecular mechanism].

C X Li, N B Zheng, C G Wang, Z C Gong.

Oral cancer, as one kind of mucosal epithelial tumor, constitutes approximately 2% of all cancers, while the most common type, oral squamous cell carcinoma (OSCC) represents around 90% histopathology of oral cancers. Although the treatment of OSCC has been improved in recent 20 years, its 5-year survival rate has not raised significantly. The crux to improve the survival rate and prognosis of OSCC patients lies in the early diagnosis and intervention of this disease. Hence, exploring new diagnostic and therapeutic strategies for OSCC is therefore an urgent priority. Exosomes, the small membrane vesicles originated from endosomes, have been detected in a wide array of bodily fluids. Exosomes have biological properties of derived cells based on containing a diversity of proteins, lipids, DNA fragments, mRNAs, and non-coding RNAs, including microRNAs, long non-coding RNAs, piRNAs, circular RNAs, tsRNAs, and ribosomal RNAs, which are delivered to neighboring cells or even transported to distant sites. They participate in cellular communication as well as play an important role in many diseases and immune response. Exosomes have been associated with the tumorigenesis of OSCC, promoting the proliferation, colonization, and metastasis of OSCC by transferring their cargos to the target cells. Furthermore, exosomes participate in the regulation of the tumor microenvironment to affect cancer progression in vivo. In this review, we summarize the crucial role of exosomes in the tumorigenesis and progression of OSCC and discuss the potential clinical application of exosomes in OSCC treatment.

DOI: https://doi.org/10.3760/cma.j.cn112144-20251015-00405
Crit Rev Oncol Hematol. 2025 Nov 26. pii: S1040-8428(25)00443-3. [Epub ahead of print] 105055

Comparison of the therapeutic potential of exosomes derived from different cells for the treatment of prostate cancer.

Farhood Khaleghi Mehr, Nikoo Emtiazi, Ehsan Zolfi, Yasaman Moradi.

  Prostate cancer (PCa) is a primary cause of male cancer death, underlining the crucial need for new therapies. Natural nanovesicles known as exosomes (EXOs) have shown great promise as therapeutic vectors due to their excellent biocompatibility, minimal immunogenicity, and inherent capacity to carry bioactive cargo. Different cell types may produce these vesicles, and each one imparts unique biological characteristics and therapeutic processes. This review compares the therapeutic potential of EXOs obtained from three primary sources for the treatment of PCa. The usefulness of mesenchymal stem cell-derived EXOs (MSC-EXOs), which leverage their inherent tumor tropism to serve as naturally occurring delivery vehicles for therapeutic agents, is critically examined. We investigate the potential of immune cell-derived EXOs (IC-EXOs) as cytotoxic agents or cell-free vaccines that effectively activate anti-tumor immunity. We also discuss the paradoxical role of tumor-derived EXOs (TEXs), which can serve as vaccine antigens or as tools for liquid biopsy, despite their role in cancer development. We highlight the unique benefits, drawbacks, and best therapeutic settings of these platforms by combining evidence from multiple platforms. Lastly, we address crucial clinical translation issues, such as manufacturing and standardization, and offer a framework for selecting the best EXO source in the evolving field of PCa treatment based on specific therapeutic goals.

Keywords:  Exosomes; Immune cells; Prostate cancer; Treatment; Tumor-derived exosomes; mesenchymal stem cells

DOI:  https://doi.org/10.1016/j.critrevonc.2025.105055
Clin Chim Acta. 2025 Nov 25. pii: S0009-8981(25)00616-3. [Epub ahead of print] 120737

Exercise-induced modulation of circulating and exosomal microRNAs and long non-coding RNAs: Molecular signatures in cancer diagnosis, prevention and therapy.

Zizhuo Wang, Qiaonan Chen, Kyung Hwan Choi.

  Physical exercise has emerged as a powerful modulator of molecular pathways involved in cancer development, progression, and therapeutic response. Recent evidence highlights the pivotal role of circulating and exosomal non-coding RNAs-including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs)-as mediators linking exercise to systemic and tumor-specific adaptations. These molecules regulate key processes such as cell proliferation, apoptosis, angiogenesis, inflammation, and immune modulation, thereby influencing the tumor microenvironment and overall cancer trajectory. Exercise-induced alterations in circulating and exosomal miRNAs and lncRNAs have been shown to reflect molecular reprogramming at both systemic and cellular levels, suggesting their potential as minimally invasive biomarkers for cancer diagnosis, prognosis, prevention, and treatment monitoring. Furthermore, exosomal non-coding RNAs serve as intercellular communicators, transferring exercise-mediated molecular signals to target tissues, which may contribute to improved therapeutic efficacy and reduced tumor progression. This review synthesizes current evidence on how different exercise modalities modulate circulating and exosomal miRNAs and lncRNAs in cancer, emphasizing their diagnostic and prognostic potential and the underlying molecular mechanisms. Understanding these interactions provides novel insights into how physical activity can be harnessed as an adjuvant strategy in precision oncology, paving the way for predictive, preventive, and personalized approaches to cancer management.

Keywords:  Cancer; Exercise; Exosome; Progression; ncRNAs

DOI:  https://doi.org/10.1016/j.cca.2025.120737
Biomed Pharmacother. 2025 Nov 27. pii: S0753-3322(25)01009-1. [Epub ahead of print]193 118815

Tumor-derived extracellular vesicles: Bridging communication and next-generation theranostics.

Jace Chen, Apple Verdiell, Carlos Formoso, Myles Luciano, Celine Chen, Abhimanyu Thakur.

  Cancer remains one of the leading causes of mortality worldwide, and despite advancements in therapeutic strategies-including chemotherapy, radiotherapy, immunotherapy, surgery, hormone therapy, and targeted therapy-a definitive cure remains elusive. In recent years, tumor-derived extracellular vesicles (TD-EVs) have garnered attention due to their critical roles in tumorigenesis, angiogenesis, and metastasis. Generated via biogenesis pathways involving the endosomal sorting complex required for transport (ESCRT), TD-EVs facilitate diverse mechanisms that promote tumor growth and survival. These include the induction of epithelial-mesenchymal transition (EMT), stimulation of angiogenesis, suppression of natural killer (NK) and T cell activity, promotion of M2 macrophage polarization, and facilitation of metastasis. Beyond their tumor-promoting functions, TD-EVs also hold promise as diagnostic and therapeutic tools. For example, EV PD-L1 has emerged as a biomarker for the liquid biopsy, reflecting tumor immune evasion, while engineered TD-EVs loaded with therapeutic cargos such as siRNAs or chemotherapeutic agents have shown potential in targeted tumor delivery. Their presence in bodily fluids and selective enrichment of tumor-specific cargo position them as valuable candidates for liquid biopsy applications, enabling non-invasive monitoring of disease progression and treatment responses. Furthermore, engineered TD-EVs are being explored as delivery systems for chemotherapeutics, RNA interference molecules, and gene-editing tools. Despite these advances, different challenges hinder the clinical translation of TD-EV-based applications. These include the heterogeneity of EV populations, lack of standardized isolation and characterization protocols, and difficulty in distinguishing TD-EVs from normal EVs in complex biological samples. Key obstacles also include the pronounced heterogeneity of EV populations and the lack of standardized isolation and characterization protocols. This review explores the multifaceted roles of TD-EVs in cancer biology and their potential utility in diagnosis, prognosis, and therapeutic intervention.

Keywords:  Cancer; EV-based therapeutics; Exosomes; Extracellular vesicles; Liquid biopsy; Theranostic

DOI:  https://doi.org/10.1016/j.biopha.2025.118815
Cell Immunol. 2025 Nov 19. pii: S0008-8749(25)00140-6. [Epub ahead of print]420-421 105054

Exosomes derived from ovarian cancer promote the progression of ovarian cancer through macrophage M2 polarization mediated by the THBS1/TGFBI signaling axis.

Linlin Yang, Yue Jia, Ying Liu, Shaojia Wang, Shufen Tan, Youqin Ruan, Lingfeng Zhao, He Zhao, Ruolan Xu, Chunyan Ding, Hui Liu, Yan Qin, Haijuan Zhao, Xinyue Feng, Changyi Zeng, Yuye Li, Xiang Meng, Hongying Yang.

   BACKGROUND: Tumor-derived exosomes play a critical role in facilitating intercellular communication between cancer cells and tumor-associated macrophages (TAMs). Nevertheless, the precise molecular mechanisms underlying exosome-mediated interactions specifically in ovarian cancer remain incompletely elucidated.
METHODS: TAMs were treated with exosomes isolated from clinical ovarian cancer specimens. Macrophage polarization was assessed using qRT-PCR, and western blot analysis. RNA sequencing was employed to identify key genes within the exosomes. The malignant phenotype of ovarian cancer cells was evaluated through cell counting kit-8 (CCK-8), Transwell assay, and wound-healing assays.
RESULTS: Our findings showed that exosomes derived from both early and late-stage malignant ovarian cancer tissues induced the upregulation of all M2 macrophage markers and the downregulation of M1 markers. RNA sequencing analysis identified thrombospondin-1 (THBS1) as a potential pivotal gene influencing exosome-regulated TAM polarization. THBS1 knockdown within exosomes inhibited the polarization of TAMs toward the M2 phenotype and concurrently decreased transforming growth factor beta induced (TGFBI) expression in macrophages. Notably, TGFBI knockdown in TAM reversed the M2 polarization induced by ovarian cancer cells-derived exosomes. In vivo, ovarian cancer cell-derived exosomes facilitate cancer progression, concomitantly increasing the polarization of M2 macrophages and upregulating THBS1 and TGFBI expression within tumor tissues.
CONCLUSION: THBS1, carried by ovarian cancer-derived exosomes, promotes M2 polarization of TAMs by modulating TGFBI expression. The subsequent M2 polarization of TAMs contributes to the establishment of an immunosuppressive tumor microenvironment, thereby facilitating disease progression. Consequently, targeting the exosome-mediated signaling axis between cancer cells and macrophages represents a promising avenue for developing novel therapeutic interventions.

Keywords:  Exosomes; Macrophage polarization; Ovarian cancer; TGFBI; THBS1

DOI:  https://doi.org/10.1016/j.cellimm.2025.105054
Sci Rep. 2025 Nov 27.

Plasma-derived exosomal tRF-3004a as a diagnostic biomarker for colorectal cancer.

Manli Zhou, Xiaoqian Yu, Jing Zhang, Zixin Huang, Sisi Feng, Xiaomin Xiao, Chunlin Ou, Baiyun Zhong.

  Transfer RNA-derived small RNAs (tsRNAs) play crucial regulatory roles in tumour biology; however, their potential as biomarkers for colorectal cancer (CRC) remains underexplored. Plasma samples from 123 patients with CRC and 79 healthy controls (HCs) were collected for this study. Exosomes were extracted from plasma, validated, and tRF-3004a levels were detected using quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between plasma-derived exosomal tRF-3004a expression levels and clinicopathological parameters was analysed using the chi-square test. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of plasma-derived exosomal tRF-3004a. The results showed that compared with HCs, plasma-derived exosomal tRF-3004a was significantly elevated in patients with CRC and decreased after surgery. Moreover, high tRF-3004a expression was significantly associated with lymph node metastasis, tumour node-metastasis staging, carcinoembryonic antigen (CEA) levels, and nerve/vascular invasion in patients with CRC. ROC analysis revealed that plasma-derived exosomal tRF-3004a demonstrated promising diagnostic utility for CRC, with an area under the curve (AUC) of 0.819 (sensitivity, 0.691; specificity, 0.861). The combination of CEA and carbohydrate antigen 19 - 9 (CA19-9) levels increased the AUC to 0.867. The results of this study demonstrate that plasma-derived exosomal tRF-3004a may serve as a novel diagnostic biomarker for CRC.

Keywords:  Diagnosis; Exosomes; Liquid biopsy; Plasma; Transfer RNA-derived small RNAs

DOI:  https://doi.org/10.1038/s41598-025-30113-2