bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2023‒08‒20
nine papers selected by
Muhammad Rizwan
COMSATS University
  1. Clinical Theranostics Trademark of Exosome in Glioblastoma Metastasis.
  2. The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy.
  3. miR-4780 Derived from N2-Like Neutrophil Exosome Aggravates Epithelial-Mesenchymal Transition and Angiogenesis in Colorectal Cancer.
  4. The value of urinary exosomal lncRNA SNHG16 as a diagnostic biomarker for bladder cancer.
  5. Downregulation of cancer-associated fibroblast exosome-derived miR-29b-1-5p restrains vasculogenic mimicry and apoptosis while accelerating migration and invasion of gastric cancer cells via immunoglobulin domain-containing 1/zonula occluden-1 axis.
  6. Extracellular vesicles targeting tumor microenvironment in ovarian cancer.
  7. Role of exosomal miRNA-19a/19b and PTEN in brain tumor diagnosis.
  8. The extracellular vesicles targeting tumor microenvironment: a promising therapeutic strategy for melanoma.
  9. Exosome-transported circHDAC1_004 Promotes Proliferation, Migration, and Angiogenesis of Hepatocellular Carcinoma by the miR-361-3p/NACC1 Axis.
  1. ACS Biomater Sci Eng. 2023 Aug 14.
    Clinical Theranostics Trademark of Exosome in Glioblastoma Metastasis.
    Sagnik Nag, Bikramjit Bhattacharya, Swagata Dutta, Debashmita Mandal, Sayantanee Mukherjee, Krishnan Anand, Rajalakshmanan Eswaramoorthy, Nanasaheb Thorat, Saurabh Kumar Jha, Sukhamoy Gorai.
      Glioblastoma (GBM) is an aggressive type of cancer that has led to the death of a large population. The traditional approach fails to develop a solution for GBM's suffering life. Extensive research into tumor microenvironments (TME) indicates that TME extracellular vesicles (EVs) play a vital role in cancer development and progression. EVs are classified into microvacuoles, apoptotic bodies, and exosomes. Exosomes are the most highlighted domains in cancer research. GBM cell-derived exosomes participate in multiple cancer progression events such as immune suppression, angiogenesis, premetastatic niche formation (PMN), ECM (extracellular matrix), EMT (epithelial-to-mesenchymal transition), metastasis, cancer stem cell development and therapeutic and drug resistance. GBM exosomes also carry the signature of a glioblastoma-related status. The exosome-based GBM examination is part of the new generation of liquid biopsy. It also solved early diagnostic limitations in GBM. Traditional therapeutic approaches do not cross the blood-brain barrier (BBB). Exosomes are a game changer in GBM treatment and it is emerging as a potential platform for effective, efficient, and specific therapeutic development. In this review, we have explored the exosome-GBM interlink, the clinical impact of exosomes on GBM biomarkers, the therapeutics signature of exosomes in GBM, exosome-based research challenges, and future directions in GBM. Therefore, the GBM-derived exosomes offer unique therapeutic opportunities, which are currently under preclinical and clinical testing.
    Keywords:  biomarker; exosome; glioblastoma; metastasis; therapeutic
    DOI:  https://doi.org/10.1021/acsbiomaterials.3c00212
  2. Genes Dis. 2024 Jan;11(1): 321-334
    The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy.
    Md Rakibul Alam, Md Mizanur Rahman, Zhiguo Li.
      Exosomes are small membrane vesicles containing microRNA, RNA, DNA fragments, and proteins that are transferred from donor cells to recipient cells. Tumor cells release exosomes to reprogram the factors associated with the tumor microenvironment (TME) causing tumor metastasis and immune escape. Emerging evidence revealed that cancer cell-derived exosomes carry immune inhibitory molecule program death ligand 1 (PD-L1) that binds with receptor program death protein 1 (PD-1) and promote tumor progression by escaping immune response. Currently, some FDA-approved monoclonal antibodies are clinically used for cancer treatment by blocking PD-1/PD-L1 interaction. Despite notable treatment outcomes, some patients show poor drug response. Exosomal PD-L1 plays a vital role in lowering the treatment response, showing resistance to PD-1/PD-L1 blockage therapy through recapitulating the effect of cell surface PD-L1. To enhance therapeutic response, inhibition of exosomal PD-L1 is required. Calcium signaling is the central regulator of tumorigenesis and can regulate exosome biogenesis and secretion by modulating Rab GTPase family and membrane fusion factors. Immune checkpoints are also connected with calcium signaling and calcium channel blockers like amlodipine, nifedipine, lercanidipine, diltiazem, and verapamil were also reported to suppress cellular PD-L1 expression. Therefore, to enhance the PD-1/PD-L1 blockage therapy response, the reduction of exosomal PD-L1 secretion from cancer cells is in our therapeutic consideration. In this review, we proposed a therapeutic strategy by targeting calcium signaling to inhibit the expression of PD-L1-containing exosome levels that could reduce the anti-PD-1/PD-L1 therapy resistance and increase the patient's drug response rate.
    Keywords:  CD8+T cells; Calcium signaling; Exosomal PD-L1; Exosomes biogenesis; Immunosuppression; Immunotherapy
    DOI:  https://doi.org/10.1016/j.gendis.2023.01.026
  3. Stem Cells Int. 2023 ;2023 2759679
    miR-4780 Derived from N2-Like Neutrophil Exosome Aggravates Epithelial-Mesenchymal Transition and Angiogenesis in Colorectal Cancer.
    Liang Wang, Yuqiang Shan, Sixin Zheng, Jiangtao Li, Peng Cui.
      Despite significant advances in diagnostic methods and treatment strategies, the prognosis for patients with advanced colon cancer remains poor, and mortality rates are often high due to metastasis. Increasing evidence showed that it is of significant importance to investigate how the tumor microenvironment participates in the development of colorectal cancer (CRC). In this manuscript, neutrophils were sequentially stimulated with all-trans retinoic acid and transforming growth factor-β in turn to induce the neutrophil polarization. Differentially expressed miRNA in neutrophil exosomes have been sequenced by microarray profile, and the effect of N2-like neutrophil-derived exosomal miR-4780 on epithelial-mesenchymal transition (EMT) and angiogenesis was investigated. In our results, we found that neutrophils were enriched in CRC tumor tissue and that CD11b expression correlated with tumor site and serous membrane invasion. At the same time, we demonstrated that internalization of N2 exosomes exacerbated the viability, migration, and invasion of CRC cell lines and inhibited apoptosis. To further investigate the molecular mechanism, we analyzed the miRNA expression profile in the N2-like neutrophils, which led to the selection of hsa-miR-4780 for the subsequent experiment. The overexpression of miR-4780 from N2-like neutrophil-derived exosomes exacerbated EMT and angiogenesis. Moreover, miR-4780 can regulate its target gene SOX11 to effect EMT and angiogenesis in CRC cell lines. CRC with liver metastasis model also validated that aberrant expression of miR-4780 in N2-like neutrophil exosomes exacerbated tumor metastasis and development of tumor via EMT and angiogenesis. In conclusion, our current findings reveal an important mechanism by which mR-4780 from N2-like neutrophil exosomes exacerbates tumor metastasis and progression via EMT and angiogenesis.
    DOI:  https://doi.org/10.1155/2023/2759679
  4. Mol Biol Rep. 2023 Aug 17.
    The value of urinary exosomal lncRNA SNHG16 as a diagnostic biomarker for bladder cancer.
    Chengyi Liu, Pengcheng Xu, Song Shao, Fang Wang, Zhiwen Zheng, Shuangjie Li, Wei Liu, Guangyuan Li.
      OBJECTIVE: To detect the expression level of urinary exosomal lncRNA SNHG16 in patients with bladder cancer and healthy individuals and explore its clinical application value in the diagnosis of bladder cancer.METHODS: Urine samples were collected from 42 patients with bladder cancer and 42 healthy volunteers who visited Lu'an Hospital of Anhui Medical University and the Second Hospital of Tianjin Medical University from January 2020 to December 2022. The expression levels of lncRNA SNHG16 in urinary exosomes of the two groups were detected by RT‒qPCR, and their correlation with clinical pathological parameters of bladder cancer patients was analysed. An Receiver Operating Characteristic(ROC) curve was drawn to analyse the diagnostic value of urinary exosomal lncRNA SNHG16 for bladder cancer and compared with urinary cytology.
    RESULTS: The expression of urinary exosomal lncRNA SNHG16 in patients with bladder cancer was significantly higher (P < 0.05), and the expression level had no correlation with the age, sex, pathological T stage, pathological grade, or tumour size of bladder cancer patients (P > 0.05). The Area Under Curve(AUC) of urinary exosomal lncRNA SNHG16 in diagnosing bladder cancer was 0.791, which was superior to that of urinary cytology (AUC = 0.597).
    CONCLUSION: Urinary exosomal lncRNA SNHG16 with high expression can serve as a potential diagnostic biological marker for bladder cancer.
    Keywords:  Biomarker; Bladder cancer; Diagnosis; Urine exosome; lncRNA SNHG16
    DOI:  https://doi.org/10.1007/s11033-023-08667-z
  5. Cell Cycle. 2023 Aug 16. 1-20
    Downregulation of cancer-associated fibroblast exosome-derived miR-29b-1-5p restrains vasculogenic mimicry and apoptosis while accelerating migration and invasion of gastric cancer cells via immunoglobulin domain-containing 1/zonula occluden-1 axis.
    Chenqu Wu, Deming Li, Xun Cheng, Hao Gu, Yanqing Qian, Li Feng.
      Background: Cancer-associated fibroblast (CAF) exosomal miRNAs have gradually a hot spot in cancer therapy. This study mainly explores the effect of CAF-derived exosomal miR-29b-1-5p on gastric cancer (GC) cells.Methods: CAFs and exosomes were identified by Western blot and transmission electron microscopy. CAF-derived exosomes-GC cells co-culture systems were constructed. Effects of CAF-derived exosomal miR-29b-1-5p on GC cells were determined by cell counting kit-8, flow cytometry, wound healing, Transwell assays and Western blot. The relationship between miR-29b-1-5p and immunoglobulin domain-containing 1 (VSIG1) was assessed by TargetScan, dual-luciferase reporter and RNA immunoprecipitation (RIP) experiments. The interaction between VSIG1 and zonula occluden-1 (ZO-1) was detected by co-immunoprecipitation. Expressions of miR-29b-1-5p, VSIG1 and ZO-1 were determined by quantitative real-time PCR. Vascular mimicry (VM) was detected using immunohistochemistry and tube formation assays. Rescue experiments and xenograft tumor assays were used to further determine the effect of CAF-derived exosomal miR-29b-1-5p/VSIG1 on GC.Results: VM structure, upregulation of miR-29b-1-5p, and downregulation of VSIG1 and ZO-1 were shown in GC tissues. MiR-29b-1-5p targeted VSIG1, which interacted with ZO-1. CAF-derived exosomal miR-29b-1-5p inhibitor suppressed the viability, migration, invasion and VM formation, but promoted the apoptosis of GC cells. MiR-29b-1-5p inhibitor increased levels of VSIG1, ZO-1 and E-cadherin, whilst decreasing levels of VE-cadherin, N-cadherin and Vimentin in vitro and in vivo, which however was partially reversed by shVSIG1. Downregulation of CAF-derived exosomal miR-29b-1-5p impeded GC tumorigenesis and VM structure in vivo by upregulating VSIG1/ZO-1 expression.Conclusion: Downregulation of CAF-derived exosomal miR-29b-1-5p inhibits GC progression via VSIG1/ZO-1 axis.
    Keywords:  Cancer-associated fibroblast; MiR-29b-1-5p; exosome, VSIG1; gastric cancer
    DOI:  https://doi.org/10.1080/15384101.2023.2231740
  6. Int J Biol Macromol. 2023 Aug 11. pii: S0141-8130(23)03196-3. [Epub ahead of print] 126300
    Extracellular vesicles targeting tumor microenvironment in ovarian cancer.
    Chunmei Zhang, Meiying Qin.
      Ovarian cancer (OC) is a prevalent neoplastic condition affecting women. Extracellular vesicles (EVs), nano-sized membrane vesicles, are secreted by various cells in both physiological and pathological states. The profound interplay between EVs and the tumor microenvironment (TME) in ovarian cancer is crucial. In this review, we explores the pivotal role of EVs in facilitating intercellular communication between cancer cells and the TME, emphasizing the potential of EVs as promising diagnostic markers and innovative therapeutic targets for ovarian cancer. The comprehensive analysis outlines the specific mechanisms by which EVs engage in communication with the constituents of the TME, including the modulation of tumor growth through EVs carrying matrix metalloproteinases (MMPs) and EV-mediated inhibition of angiogenesis, among other factors. Additionally, the we discuss the potential clinical applications of EVs that target the TME in ovarian cancer, encompassing the establishment of novel treatment strategies and the identification of novel biomarkers for early detection and prognosis. Finally, this review identifies novel strategies for therapeutic interventions, such as utilizing EVs as carriers for drug delivery and targeting specific EV-mediated signaling pathways. In summary, this manuscript offers valuable insights into the role of EVs in ovarian cancer and highlights the significance of comprehending intercellular communication in the realm of cancer biology.
    Keywords:  Extracellular vesicles; Intercommunication; Ovarian cancer; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.ijbiomac.2023.126300
  7. Future Oncol. 2023 Jul;19(22): 1563-1576
    Role of exosomal miRNA-19a/19b and PTEN in brain tumor diagnosis.
    Nida Sarosh Ashraf, Ishrat Mahjabeen, Muhammad Zahid Hussain, Muhammad Rizwan, Maryam Arshad, Azhar Mehmood, Muhammad Shahbaz Haris, Mahmood Akhtar Kayani.
      Aim: The current study was designed to evaluate the diagnostic significance of the exosomal miRNAs miR-19a and miR-19b and the PTEN gene in brain tumor patients versus controls. Methods: Exosomes were extracted from the serum samples of 400 brain tumor patients and 400 healthy controls. The exosomes were characterized by scanning electron microscopy, dynamic light scattering and ELISA. Quantitative PCR was used to analyze selected exosome miRNAs and gene expression levels. Results: Analysis showed significant deregulated expression of miR-19a (p < 0.0001), miR-19b (p < 0.0001) and PTEN (p < 0.001) in patients versus controls. Spearman correlation showed a significant correlation among the selected exosomal miRNAs and the PTEN gene. Conclusion: Receiver operating characteristic curve analysis showed the good diagnostic value of exosomal miRNAs and the PTEN gene in brain tumor patients.
    Keywords:  PTEN; biomarker; brain tumor; exosome; glioblastoma; miR-17-92 cluster; miR-19a; miR-19b
    DOI:  https://doi.org/10.2217/fon-2023-0234
  8. Front Immunol. 2023 ;14 1200249
    The extracellular vesicles targeting tumor microenvironment: a promising therapeutic strategy for melanoma.
    Yongmin Li, Fei Liu.
      Extracellular vesicles (EVs) are small particles secreted by numerous cell types and circulate in almost all body fluids, acting as crucial messengers for cell-to-cell communication. EVs involves multiple physiological and pathological processes, including tumor progression, via their multiple cargoes. Therefore, EVs have become attractive candidates for the treatment of tumor, including melanoma. Notably, due to the crucial role of the tumor microenvironment (TME) in promoting tumor malignant phenotype, and the close intercellular communication in TME, EVs-based therapy by targeting TME has become a cutting-edge and prospective strategy for inhibiting melanoma progression and strengthening the anti-tumor immunity. In this review, we aimed to summarize and discuss the role of therapeutic EVs, which target the components of TME in melanoma, thereby providing insights into these promising clinical strategies for the treatment of melanoma patients.
    Keywords:  cancer; extracellular vesicles; immunotherapy; melanoma; tumor microenvironment
    DOI:  https://doi.org/10.3389/fimmu.2023.1200249
  9. J Clin Transl Hepatol. 2023 Oct 28. 11(5): 1079-1093
    Exosome-transported circHDAC1_004 Promotes Proliferation, Migration, and Angiogenesis of Hepatocellular Carcinoma by the miR-361-3p/NACC1 Axis.
    Bin Xu, Wenbo Jia, Yanzhi Feng, Jinyi Wang, Jing Wang, Deming Zhu, Chao Xu, Litao Liang, Wenzhou Ding, Yongping Zhou, Lianbao Kong.
      Background and Aims: Hepatocellular carcinoma (HCC) is among the most common malignant tumors globally. Circular RNAs (circRNAs), as a type of noncoding RNAs, reportedly participate in various tumor biological processes. However, the role of circHDAC1_004 in HCC remains unclear. Thus, we aimed to explore the role and the underlying mechanisms of circHDAC1_004 in the development and progression of HCC.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect circHDAC1_004 expression (circ_0005339) in HCC. Sanger sequencing and agarose gel electrophoresis were used to determine the structure of circHDAC1_004. In vitro and in vivo experiments were used to determine the biological function of circHDAC1_004 in HCC. Herein, qRT-PCR, RNA immunoprecipitation, western blotting, and a luciferase reporter assay were used to explore the relationships among circHDAC1_004, miR-361-3p, and NACC1.
    Results: circHDAC1_004 was upregulated in HCC and significantly associated with poor overall survival. circHDAC1_004 promoted HCC cell proliferation, stemness, migration, and invasion. In addition, circHDAC1_004 upregulated human umbilical vein endothelial cells (HUVECs) and promoted angiogenesis through exosomes. circHDAC1_004 promoted NACC1 expression and stimulated the epithelial-mesenchymal transition pathway by sponging miR-361-3p.
    Conclusions: We found that circHDAC1_004 overexpression enhanced the proliferation, stemness, and metastasis of HCC via the miR-361-3p/NACC1 axis and promoted HCC angiogenesis through exosomes. Our findings may help develop a possible therapeutic strategy for HCC.
    Keywords:  Angiogenesis; Epithelial-mesenchymal transformation; Exosome; Hepatocellular carcinoma; Stemness; circHDAC1_004
    DOI:  https://doi.org/10.14218/JCTH.2022.00097
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