bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2023–12–17
nineteen papers selected by
Muhammad Rizwan, COMSATS University
  1. Tumor-derived exosomal miR-1247-3p promotes angiogenesis in bladder cancer by targeting FOXO1.
  2. The Function, Underlying Mechanism and Clinical Potential of Exosomes in Colorectal Cancer.
  3. Regulatory mechanism and promising clinical application of exosomal circular RNA in gastric cancer.
  4. Exosomes-derived miR-548am-5p promotes colorectal cancer progression.
  5. Role of exosomes in metastasis and therapeutic resistance in esophageal cancer.
  6. Extracellular Vesicles: Biological Packages That Modulate Tumor Cell Invasion.
  7. Mesenchymal stem cells-derived exosomes: novel carriers for nanoparticle to combat cancer.
  8. Exosomal long non-coding RNAs in glioblastoma.
  9. Metabolic labelling of a subpopulation of small extracellular vesicles using a fluorescent palmitic acid analogue.
  10. Increased Plasmatic Levels of Exosomes Are Significantly Related to Relapse Rate in Patients with Oral Squamous Cell Carcinoma: A Cohort Study.
  11. Extracellular vesicles-associated miRNAs in triple-negative breast cancer: From tumor biology to clinical relevance.
  12. Biological, diagnostic and therapeutic implications of exosomes in glioma.
  13. Exosome-mediated delivery of miR-519e-5p promotes malignant tumor phenotype and CD8+ T-cell exhaustion in metastatic PTC.
  14. Identifying tumor cell-released extracellular vesicles as biomarkers for breast cancer diagnosis by a three-dimensional hydrogel-based electrochemical immunosensor.
  15. Emerging Microfluidic Tools for Simultaneous Exosomes and Cargo Biosensing in Liquid Biopsy: New Integrated Miniaturized FFF-Assisted Approach for Colon Cancer Diagnosis.
  16. Exosomes and their engineering strategies, delivery systems, and biomedical applications.
  17. Extracellular vesicles remodel tumor environment for cancer immunotherapy.
  18. Cellular Responses to Extracellular Vesicles as Potential Markers of Colorectal Cancer Progression.
  19. Novel lncRNA Gm33149 modulates metastatic heterogeneity in melanoma by regulating the miR-5623-3p/Wnt axis via exosomal transfer.
  1. Cancer Biol Ther. 2024 Dec 31. 25(1): 2290033
    Tumor-derived exosomal miR-1247-3p promotes angiogenesis in bladder cancer by targeting FOXO1.
    Zonglai Liu, Dan Du, Shizhong Zhang.
      Tumor-derived exosomes are highly correlated with tumor progression and angiogenesis. This study was designed to probe the role of tumor-derived exosomal miR-1247-3p in mediating the angiogenesis in bladder cancer. Exosomes isolation from the culture medium of normal or bladder cancer cell lines was performed using a differential centrifugation method. miR-1247-3p expression in exosomes and cells was detected by quantitative real-time PCR (qRT-PCR). The effect of exosomes on the angiogenesis of human umbilical vein endothelial cells (HUVECs) was assessed using cell counting kit-8 (CCK-8), transwell and tube formation assays. The interaction between miR-1247-3p and forkhead box protein O1 (FOXO1) was studied using luciferase reporter and RNA pull down assays. Exosomes were successfully isolated from T24, UM-UC-3, and SV-HUC-1 cells, as confirmed by corresponding identifications. Functional experiments revealed that exosomes derived from T24 and UM-UC-3 cells significantly enhanced the abilities of proliferation, migration, angiogenesis, and vascular endothelial-derived growth factor (VEGF) secretion in HUVECs. miR-1247-3p was highly expressed in exosomes derived from T24 and UM-UC-3 cells, and exosomes derived from miR-1247-3p inhibitor-transfected cells reduced HUVEC viability, migration, tube formation, and VEGF level. FOXO1 was confirmed as a direct target of miR-1247-3p. Rescue assays suggested that the effect of miR-1247-3p inhibition on the viability, migration, and angiogenesis of HUVECs was partly abrogated by the knockdown of FOXO1. Our data suggest that miR-1247-3p is up-regulated in tumor-derived exosomes, thereby inhibiting FOXO1 expression and facilitating angiogenesis in bladder cancer.
    Keywords:  Bladder cancer; FOXO1; angiogenesis; exosomes; miR-1247-3p
    DOI:  https://doi.org/10.1080/15384047.2023.2290033
  2. Front Biosci (Landmark Ed). 2023 Nov 24. 28(11): 302
    The Function, Underlying Mechanism and Clinical Potential of Exosomes in Colorectal Cancer.
    Jinhong Han, Shuai Ma, Yao Zhao, Bingxian Wang, Shuang Ding, Yuhan Hu.
      Colorectal cancer (CRC) is a lethal malignancy worldwide. Exosomes are extracellular vesicles derived from the endosomal pathway of nearly all cells and can be found in body fluids. They can be considered an intercellular system in the human body that can mediate near- and long-distance intercellular communication due to their features and functions. Investigations have revealed that exosomes are participated in different processes, physiologically and pathologically, especially in cancer. However, the clinical value of exosomes and their mechanisms of action in CRC are unclear and have not been systematically assessed. The purpose of this review is to discuss how exosomes play a role in the occurrence and development of CRC, with a particular focus on the functions and underlying mechanisms of tumor-derived exosomes as well as non-tumor-derived exosomes. We also describe the evidence that exosomes can be used as diagnostic and prognostic markers for CRC. In addition, the possibilities of exosomes in CRC clinical transformation are also discussed.
    Keywords:  biomarker; clinical transformation; colorectal cancer; diagnosis; exosome
    DOI:  https://doi.org/10.31083/j.fbl2811302
  3. Front Oncol. 2023 ;13 1236679
    Regulatory mechanism and promising clinical application of exosomal circular RNA in gastric cancer.
    Ming Han, Mengyuan Zhang, Mei Qi, Yue Zhou, Fulong Li, Shengquan Fang.
      Gastric cancer (GC) is one of the most common malignancies worldwide and the leading cause of cancer-related deaths. Exosomes are nanoscale extracellular vesicles secreted by a variety of cells and play an important role in cellular communication and epigenetics by transporting bioactive substances in the tumor microenvironment (TME). Circular RNA (circRNA) is a type of non-coding RNA (ncRNA) with a specific structure, which is widely enriched in exosomes and is involved in various pathophysiological processes mediated by exosomes. Exosomal circRNAs play a critical role in the development of GC by regulating epithelial-mesenchymal transition (EMT), angiogenesis, proliferation, invasion, migration, and metastasis of GC. Given the biological characteristics of exosomal circRNAs, they have more significant diagnostic sensitivity and specificity in the clinic and may become biomarkers for GC diagnosis and prognosis. In this review, we briefly describe the biogenesis of exosomes and circRNAs and their biological functions, comprehensively summarize the mechanisms of exosomal circRNAs in the development of GC and chemotherapy resistance, and finally, we discuss the potential clinical application value and challenges of exosomal circRNAs in GC.
    Keywords:  biomarkers; chemotherapy resistance; epithelial-mesenchymal transition; exosomal circRNAs; gastric cancer
    DOI:  https://doi.org/10.3389/fonc.2023.1236679
  4. Cell Mol Biol (Noisy-le-grand). 2023 Nov 30. 69(12): 104-110
    Exosomes-derived miR-548am-5p promotes colorectal cancer progression.
    Fangfang Li, Minglei Zhang, Xiaodong Yin, Wei Zhang, Haiyang Li, Chao Gao.
      Exosomes are vital modulators in intercellular communication and microRNAs (miRNAs) are enriched within exosomes. MiRNAs are important participants in affecting colorectal cancer (CRC) progression, but the influence and latent mechanism of cancer-secreted exosomal miRNAs in colorectal cancer are not fully understood. miR-548am-5p has been reported to be differentially expressed in colon cancer and is indicated as a biomarker for colon cancer diagnosis at the early stage. In this study, we aimed to explore the role of exosomes-derived miR-548am-5p in CRC development. ISH and FISH were implemented to assess miR-548am-5p expression and location in CRC. CRC cells-secreted exosomes were identified via transmission electron microscopy and western blot. Colony formation, sphere formation and flow cytometry assessed the changes in proliferation, stemness and apoptosis of CRC cells. Bioinformatic analyses and mechanical experiments verified the binding of miR-548am-5p and RAR-related orphan receptor A (RORA). Our study identified miR-548am-5p was highly expressed in CRC tissues and cells. Tumor-derived exosomes expedited CRC cell proliferation and stemness along with secreted miR-548am-5p. Moreover, miR-548am-5p inhibition suppressed CRC cell proliferation and stemness while promoting cell apoptosis. RORA was the target mRNA of miR-548am-5p. Down-regulation of RORA was discovered in CRC and its expression was repressed by CRC cell-derived exosomes. As a result, our work elucidated that tumor-derived exosomal miR-548am-5p promoted CRC cell proliferation and stemness via targeting RORA, providing a valuable sight for CRC therapy.
    DOI:  https://doi.org/10.14715/cmb/2023.69.12.17
  5. World J Gastroenterol. 2023 Nov 14. 29(42): 5699-5715
    Role of exosomes in metastasis and therapeutic resistance in esophageal cancer.
    Xing-Yu Ning, Jin-Hu Ma, Wei He, Jun-Ting Ma.
      Esophageal cancer (EC) has a high incidence and mortality rate and is emerging as one of the most common health problems globally. Owing to the lack of sensitive detection methods, uncontrollable rapid metastasis, and pervasive treatment resistance, EC is often diagnosed in advanced stages and is susceptible to local recurrence. Exosomes are important components of intercellular communication and the exosome-mediated crosstalk between the cancer and surrounding cells within the tumor microenvironment plays a crucial role in the metastasis, progression, and therapeutic resistance of EC. Considering the critical role of exosomes in tumor pathogenesis, this review focused on elucidating the impact of exosomes on EC metastasis and therapeutic resistance. Here, we summarized the relevant signaling pathways involved in these processes. In addition, we discussed the potential clinical applications of exosomes for the early diagnosis, prognosis, and treatment of EC.
    Keywords:  Esophageal cancer; Exosomes; Metastasis; Signaling pathway; Therapeutic resistance; Tumor microenvironment
    DOI:  https://doi.org/10.3748/wjg.v29.i42.5699
  6. Cancers (Basel). 2023 Nov 28. pii: 5617. [Epub ahead of print]15(23):
    Extracellular Vesicles: Biological Packages That Modulate Tumor Cell Invasion.
    Madison Schmidtmann, Crislyn D'Souza-Schorey.
      Tumor progression, from early-stage invasion to the formation of distal metastases, relies on the capacity of tumor cells to modify the extracellular matrix (ECM) and communicate with the surrounding stroma. Extracellular vesicles (EVs) provide an important means to regulate cell invasion due to the selective inclusion of cargoes such as proteases and matrix proteins into EVs that can degrade or modify the ECM. EVs have also been shown to facilitate intercellular communication in the tumor microenvironment through paracrine signaling, which can impact ECM invasion by cancer cells. Here, we describe the current knowledge of EVs as facilitators of tumor invasion by virtue of their effects on proteolytic degradation and modification of the ECM, their ability to educate the stromal cells in the tumor microenvironment, and their role as mediators of long-range communication aiding in cell invasion and matrix remodeling at secondary sites.
    Keywords:  cancer; exosomes; extracellular matrix; extracellular vesicles; metastasis; microvesicles; tumor cell invasion
    DOI:  https://doi.org/10.3390/cancers15235617
  7. Eur J Med Res. 2023 Dec 09. 28(1): 579
    Mesenchymal stem cells-derived exosomes: novel carriers for nanoparticle to combat cancer.
    Reza Abbasi, Raziye Momen Mesgin, Fereshteh Nazari-Khanamiri, Nima Abdyazdani, Zeynab Imani, Shabnam Pirnezhad Talatapeh, Aidin Nourmohammadi, Vahid Nejati, Jafar Rezaie.
       BACKGROUND: The advancement in novel cancer therapeutics brought a platform combining the properties of exosomes with nanoparticles to precision medicine. The novel therapeutic approach aim is cancer-targeted therapy. Exosomes from mesenchymal stem cells (MSCs-Exo) exhibit unique properties in cancer therapies, which makes them an ideal tool for delivering therapeutic agents into tumor cells. The key role of natural MSCs-Exo is controversial in cancer therapy; however, they can be engineered at their surface or cargo to serve as a smart drug delivery system for cancer-targeted therapy. In the last few years, researchers harnessed nanotechnology to enforce MSCs-Exo for cancer management including, tumor cell tracking, imaging, and tumor cell killing. Different nanoparticles such as gold nanoparticles have particularly been incorporated into MSCs-Exo, which showed an efficient accumulation at the site of tumor with improved anticancer impact. These findings indicate that a hybrid of exosomes-nanoparticles may serve as combination therapy for the effective removal of cancers.
    SHORT CONCLUSION: Although exhibiting impressive potential, the use of nanoparticle-loaded MSCs-Exo as a drug-delivery tool has been troubled by some challenges, therefore, translation to clinic prerequisites further scrutiny. In this review, we focus on nanoparticle-loaded MSCs-Exo as a new cancer therapy and discuss engineered MSC-Exo for target therapy.
    Keywords:  Cancer therapy; Exosomes; Mesenchymal stem cells; Nanoparticles
    DOI:  https://doi.org/10.1186/s40001-023-01556-y
  8. Clin Chim Acta. 2023 Dec 10. pii: S0009-8981(23)00507-7. [Epub ahead of print] 117705
    Exosomal long non-coding RNAs in glioblastoma.
    Mehdi Fattahi, Vahab Alamdari-Palangi, Khojaste Rahimi Jaberi, Sajad Ehtiati, Sara Ojaghi, Abbas Rahimi-Jaberi, Sadra Samavarchi Tehrani, Phuyen Dang, Ahmad Movahedpour, Seyyed Hossein Khatami.
      Glioblastoma multiforme (GBM) is the most prevalent primary tumor found in the central nervous system, accounting for 70% of all adult brain tumors. The median overall survival rate is one year post-diagnosis with treatment, and only four months without treatment. Current GBM diagnostic methods, such as magnetic resonance imaging (MRI), surgery, and brain biopsies, have limitations. These include difficulty distinguishing between tumor recurrence and post-surgical necrotic regions, and operative risks associated with obtaining histological samples through direct surgery or biopsies. Consequently, there is a need for rapid, inexpensive, and minimally invasive techniques for early diagnosis and improved subsequent treatment. Research has shown that tumor-derived exosomes containing various long non-coding RNAs (lncRNAs) play critical regulatory roles in immunomodulation, cancer metastasis, cancer development, and drug resistance in GBM. They regulate genes that enhance cancer growth and progression and alter the expression of several key signaling pathways. Due to the specificity and sensitivity of exosomal lncRNAs, they have the potential to be used as biomarkers for early diagnosis and prognosis, as well as to monitor a patient's response to chemotherapy for GBM. In this review, we discuss the role of exosomal lncRNAs in the pathogenesis of GBM and their potential clinical applications for early diagnosis.
    Keywords:  Biomarker; Diagnosis; Exosomal; GBM; Treatment; lncRNAs
    DOI:  https://doi.org/10.1016/j.cca.2023.117705
  9. J Extracell Vesicles. 2023 Dec;12(12): e12392
    Metabolic labelling of a subpopulation of small extracellular vesicles using a fluorescent palmitic acid analogue.
    Valeria Barreca, Zaira Boussadia, Deborah Polignano, Lorenzo Galli, Valentina Tirelli, Massimo Sanchez, Mario Falchi, Lucia Bertuccini, Francesca Iosi, Massimo Tatti, Massimo Sargiacomo, Maria Luisa Fiani.
      Exosomes are among the most puzzling vehicles of intercellular communication, but several crucial aspects of their biogenesis remain elusive, primarily due to the difficulty in purifying vesicles with similar sizes and densities. Here we report an effective methodology for labelling small extracellular vesicles (sEV) using Bodipy FL C16, a fluorescent palmitic acid analogue. In this study, we present compelling evidence that the fluorescent sEV population derived from Bodipy C16-labelled cells represents a discrete subpopulation of small exosomes following an intracellular pathway. Rapid cellular uptake and metabolism of Bodipy C16 resulted in the incorporation of fluorescent phospholipids into intracellular organelles specifically excluding the plasma membrane and ultimately becoming part of the exosomal membrane. Importantly, our fluorescence labelling method facilitated accurate quantification and characterization of exosomes, overcoming the limitations of nonspecific dye incorporation into heterogeneous vesicle populations. The characterization of Bodipy-labelled exosomes reveals their enrichment in tetraspanin markers, particularly CD63 and CD81, and in minor proportion CD9. Moreover, we employed nanoFACS sorting and electron microscopy to confirm the exosomal nature of Bodipy-labelled vesicles. This innovative metabolic labelling approach, based on the fate of a fatty acid, offers new avenues for investigating exosome biogenesis and functional properties in various physiological and pathological contexts.
    Keywords:  MVB; exosome biogenesis; exosomes; extracellular vesicles; lipid metabolism; sEV
    DOI:  https://doi.org/10.1002/jev2.12392
  10. Cancers (Basel). 2023 Dec 02. pii: 5693. [Epub ahead of print]15(23):
    Increased Plasmatic Levels of Exosomes Are Significantly Related to Relapse Rate in Patients with Oral Squamous Cell Carcinoma: A Cohort Study.
    Samuel Rodríguez-Zorrilla, Alejandro I Lorenzo-Pouso, Stefano Fais, Maria A Logozzi, Davide Mizzoni, Rossella Di Raimo, Alessandro Giuliani, Abel García-García, Alba Pérez-Jardón, Karem L Ortega, Ángel Martínez-González, Mario Pérez-Sayáns.
       BACKGROUND: Oral squamous cell carcinoma (OSCC) is characterized by an immunosuppressive tumor microenvironment. Their plasma-derived exosomes deliver immunomodulatory molecules and cargo that correlate significantly with clinical parameters. This study aims to assess the exosomal profile as a potential tool for early detection of relapse and long-term outcomes in OSCC patients undergoing conventional therapy.
    METHODS: 27 OSCC patients with a median 38-month follow-up were included in this study. The relationship between NTA-derived parameters and clinical pathological parameters was examined, and receiver operating characteristic (ROC) curves were utilized to evaluate the diagnostic efficacy of these values in detecting cancer relapse.
    RESULTS: Plasmatic levels of exosomes prior to surgery showed a drastic reduction after surgical intervention (8.08E vs. 1.41 × 109 particles/mL, p = 0.006). Postsurgical concentrations of exosomes were higher in patients who experienced relapse compared to those who remained disease-free (2.97 × 109 vs. 1.11 × 109 particles/mL, p = 0.046). Additionally, patients who relapsed exhibited larger exosome sizes after surgery (141.47 vs. 132.31 nm, p = 0.03). Patients with lower concentrations of exosomes prior to surgery demonstrated better disease-free survival compared to those with higher levels (p = 0.012). ROC analysis revealed an area under the curve of 0.82 for presurgical exosome concentration in identifying relapse.
    CONCLUSIONS: Presurgical exosomal plasmatic levels serve as independent predictors of early recurrence and survival in OSCC. All in all, our findings indicate that the detection of peripheral exosomes represents a novel tool for the clinical management of OSCC, with potential implications for prognosis assessment.
    Keywords:  NTA; liquid biopsy; mouth neoplasm; plasmatic exosomes; screening test
    DOI:  https://doi.org/10.3390/cancers15235693
  11. Life Sci. 2023 Dec 07. pii: S0024-3205(23)00967-0. [Epub ahead of print] 122332
    Extracellular vesicles-associated miRNAs in triple-negative breast cancer: From tumor biology to clinical relevance.
    Fernanda Costa Brandão Berti, Maria Vitoria Tofolo, Emanuelle Nunes Souza, Rafael Marchi, Larissa Miyuki Okano, Mayara Ruthes, Daiane Rosolen, Danielle Malheiros, Aline Simoneti Fonseca, Luciane Regina Cavalli.
      Breast cancer (BC), a heterogeneous group of diseases, is the most frequent type and the leading cause of cancer-related death among women worldwide. Tumor heterogeneity directly affects cancer progression and treatment, as can be evidenced by the diversity of the prognosis and treatment responses of the patients across the distinct intrinsic molecular subtypes. Triple-negative breast cancer (TNBC), which accounts for approximately 10-20 % of all diagnosed BC cases, is an aggressive BC subtype with a challenging prognosis. Current treatment options include systemic chemotherapy and/or target therapies based on PARP and PD-L1 inhibitors for eligible patients. MicroRNAs (miRNAs) have emerged as important regulatory non-coding RNAs (ncRNAs) in TNBC tumorigenesis. These molecules are present both at intracellular level, and as released into biofluids packaged into extracellular vesicles (EVs). Emerging evidence shows that EVs-associated miRNAs (EVs-miRNAs), transferred from parental cells to recipient cells, are key mediators of cell-to-cell communication. Considering their stability and abundance in several biofluids, these molecules may represent the epigenomic composition of their tumors of origin and contribute to mediate tumorigenesis similar to their intracellular counterparts. This review provides the current knowledge on EVs-miRNAs in the TNBC subtype, focusing on their role in the regulation of mRNA targets involved in the tumor phenotypes and their clinical relevance as promising biomarkers in liquid biopsies. OTHER TERMS THAT HELP DEFINE THE STUDY: Breast cancer, TNBC, TNBC tumorigenesis, miRNAs, exosomal miRNAs, candidate biomarkers.
    Keywords:  Exossomes; Extracellular vesicles; Liquid biopsy; Non-coding RNAs; Triple negative breast cancer; microRNAs
    DOI:  https://doi.org/10.1016/j.lfs.2023.122332
  12. Cancer Lett. 2023 Dec 11. pii: S0304-3835(23)00543-8. [Epub ahead of print] 216592
    Biological, diagnostic and therapeutic implications of exosomes in glioma.
    Caroline L Davidson, Raghupathy Vengoji, Maneesh Jain, Surinder K Batra, Nicole Shonka.
      Despite therapeutic advances, overall survival in glioblastoma is dismal. To optimize progress, a more detailed understanding of glioma's molecular, cellular, and intercellular pathophysiology is needed. Recent investigation has revealed a vital role for exosomes in inter-cellular signaling, tumor cell support, and regulation of the tumor microenvironment. Exosomes carry miRNAs, lncRNAs, mRNAs, proteins, immune regulatory molecules, nucleic acids, and lipids; however, the composition of exosome cargo is variable depending on the cell of origin. Specific exosomal miRNA contents such as miR-21, miR-301a, miR-151a, miR-148a, and miR-5096 are altered in high-grade glioma. Unique proteomic, genomic, and miRNA signatures of tumor exosomes have been associated with disease pathobiology, temozolomide resistance, immunosuppression, and tumor proliferation. Exosomes hold promise for tissue diagnostic glioma diagnosis and monitoring response to therapy. This review summarizes the current understanding of exosomes, their crucial role in glioma pathology, and future directions for their use in diagnosis and treatment. METHODS: The MEDLINE/PubMed database was reviewed for papers written in English and publication dates of 1981-2023, using the search string "Exosome", "Extracellular vesicles", "Glioma", "Exosomes in glioma".
    DOI:  https://doi.org/10.1016/j.canlet.2023.216592
  13. J Clin Endocrinol Metab. 2023 Dec 11. pii: dgad725. [Epub ahead of print]
    Exosome-mediated delivery of miR-519e-5p promotes malignant tumor phenotype and CD8+ T-cell exhaustion in metastatic PTC.
    Genpeng Li, Wenjie Chen, Ke Jiang, Jing Huang, Jinjing Zhong, Xiaowei Liu, Tao Wei, Rixiang Gong, Zhihui Li, Jingqiang Zhu, Hubing Shi, Jianyong Lei.
       CONTEXT: Distant metastases are the primary cause of therapy failure and mortality in patients with papillary thyroid carcinomas (PTCs). However, the underlying mechanism responsible for the initiation of tumor cell dissemination and metastasis in PTCs has rarely been investigated.
    OBJECTIVE: The aim of this study was to investigate effects and underlying molecular mechanisms of circulating exosomal microRNAs (miRNAs) in distant metastatic PTCs.
    METHODS: The most relevant circulating exosomal miRNA to distant metastatic PTCs were verified between distant metastatic PTCs and nondistant metastatic PTCs by miRNA microarray, quantitative real-time polymerase chain reaction (qRT‒PCR) assays and receiver operating characteristic (ROC) curves. The parental and recipient cells of that circulating exosomal miRNA were then explored. In vitro and in vivo experiments were further performed to elucidate the function and potential mechanisms of circulating exosomal miRNAs that contribute to the development of distant metastases.
    RESULTS: We identified that PTC-derived exosomal miR-519e-5p was significantly upregulated in the circulatory system in distant metastatic PTCs. Further tests demonstrated that PTC cells can acquire a more malignant phenotype via hnRNPA2B1 mediated sorting of tumor suppressor miR-519e-5p into exosomes to activate Wnt signaling pathway via upregulating PLAGL2. Furthermore, miR-519e-5p included in PTC-derived exosomes can be transferred to recipient CD8+ T cells and aid in tumor immune escape in distant organs through inhibiting Notch signaling pathway by downregulating NOTCH2.
    CONCLUSION: Our findings highlighted the dual role of PTC-derived exosomal miR-519e-5p in distant metastasis, which may improve our understanding of exosome-mediated distant metastatic mechanisms.
    Keywords:  Distant metastasis; exosomal miRNAs; papillary thyroid carcinomas
    DOI:  https://doi.org/10.1210/clinem/dgad725
  14. J Nanobiotechnology. 2023 Dec 07. 21(1): 467
    Identifying tumor cell-released extracellular vesicles as biomarkers for breast cancer diagnosis by a three-dimensional hydrogel-based electrochemical immunosensor.
    Yue Zhang, Deng Pan, Zhenqiang Ning, Fang Huang, Yiting Wei, Mingming Zhang, Yuanjian Zhang, Li-Xin Wang, Yanfei Shen.
      Tumor cell-released LC3+ extracellular vesicles (LC3+ EVs) participate in immunosuppression during autophagy and contribute to the occurrence and development of breast cancer. In view of the strong association between the LC3+ EVs and breast cancer, developing an effective strategy for the quantitative detection of LC3+ EVs levels with high sensitivity to identify LC3+ EVs as new biomarkers for accurate diagnosis of breast cancer is crucial, but yet not been reported. Herein, an ultrasensitive electrochemical immunosensor is presented for the quantitative determination of LC3+ EVs using a three-dimensional graphene oxide hydrogel-methylene blue composite as a redox probe, showing a low detection limit and a wide linear range. With this immunosensor, the expression levels of LC3+ EVs in various practical sample groups including different cancer cell lines, the peripheral blood of tumor-bearing mice before and after immunotherapy, and the peripheral blood from breast cancer patients with different subtypes and stages were clearly distinguished. This study demonstrated that LC3+ EVs were superior as biomarkers for the accurate diagnosis of breast cancer compared to traditional biomarkers, particularly for cancer subtype discrimination. This work would provide a new noninvasive detection tool for the early diagnosis and prognosis assessment of breast cancer in clinics.
    Keywords:  Biomarker; Breast cancer; Early diagnosis; LC3+ extracellular vesicles; cancer subtypes and stages
    DOI:  https://doi.org/10.1186/s12951-023-02180-y
  15. Sensors (Basel). 2023 Nov 27. pii: 9432. [Epub ahead of print]23(23):
    Emerging Microfluidic Tools for Simultaneous Exosomes and Cargo Biosensing in Liquid Biopsy: New Integrated Miniaturized FFF-Assisted Approach for Colon Cancer Diagnosis.
    Valentina Marassi, Stefano Giordani, Anna Placci, Angela Punzo, Cristiana Caliceti, Andrea Zattoni, Pierluigi Reschiglian, Barbara Roda, Aldo Roda.
      The early-stage diagnosis of cancer is a crucial clinical need. The inadequacies of surgery tissue biopsy have prompted a transition to a less invasive profiling of molecular biomarkers from biofluids, known as liquid biopsy. Exosomes are phospholipid bilayer vesicles present in many biofluids with a biologically active cargo, being responsible for cell-to-cell communication in biological systems. An increase in their excretion and changes in their cargo are potential diagnostic biomarkers for an array of diseases, including cancer, and they constitute a promising analyte for liquid biopsy. The number of exosomes released, the morphological properties, the membrane composition, and their content are highly related to the physiological and pathological states. The main analytical challenge to establishing liquid biopsy in clinical practice is the development of biosensors able to detect intact exosomes concentration and simultaneously analyze specific membrane biomarkers and those contained in their cargo. Before analysis, exosomes also need to be isolated from biological fluids. Microfluidic systems can address several issues present in conventional methods (i.e., ultracentrifugation, size-exclusion chromatography, ultrafiltration, and immunoaffinity capture), which are time-consuming and require a relatively high amount of sample; in addition, they can be easily integrated with biosensing systems. A critical review of emerging microfluidic-based devices for integrated biosensing approaches and following the major analytical need for accurate diagnostics is presented here. The design of a new miniaturized biosensing system is also reported. A device based on hollow-fiber flow field-flow fractionation followed by luminescence-based immunoassay is applied to isolate intact exosomes and characterize their cargo as a proof of concept for colon cancer diagnosis.
    Keywords:  colon cancer; exosomes; hollow-fiber field-flow fractionation; liquid biopsy; luminescence; microfluidic; miniaturization; reagent less biosensors
    DOI:  https://doi.org/10.3390/s23239432
  16. J Control Release. 2023 Dec 06. pii: S0168-3659(23)00782-4. [Epub ahead of print]
    Exosomes and their engineering strategies, delivery systems, and biomedical applications.
    Chunhao Yang, Yunxin Xue, Yu Duan, Chun Mao, Mimi Wan.
      Exosomes are nanoscale extracellular vesicles (30-200 nm) that can be secreted by all cell types, are intracellular in origin and have the same composition as their parent cells, play a key role in intercellular communication in organismal health and disease, and are now often used as biomarkers of disease and therapeutic agents in biomedical research. When injected locally or systemically, they have the ability to provide a variety of therapeutic effects, for example, regeneration of skin damage or restoration of cardiac function. However, direct injection of exosomes may result in their rapid clearance from the injection site.In order to maintain the biological activity of exosomes and to control the release of effective concentrations for better therapeutic efficacy during long-term disease treatment, the design of an optimized drug delivery system is necessary and different systems for the continuous delivery of exosomes have been developed. This paper first provides an overview of the biogenesis, composition and physiological function of exosomes, followed by a review of different strategies for exosome isolation and methods for engineering exosomes. In addition, this paper reviews the latest exosome delivery platforms such as micro-nanoparticles, injectable hydrogels, microneedles and scaffold patches. At the same time, the research progress and key cases of exosome delivery systems in the field of biomedical therapeutics are described. Finally, the challenges and future trends of exosome delivery are discussed.
    Keywords:  Biomaterials; Biomedical applications; Delivery systems; Exosome engineering; Exosomes
    DOI:  https://doi.org/10.1016/j.jconrel.2023.11.057
  17. Mol Cancer. 2023 Dec 13. 22(1): 203
    Extracellular vesicles remodel tumor environment for cancer immunotherapy.
    Ming Yue, Shengyun Hu, Haifeng Sun, Baojing Tuo, Bin Jia, Chen Chen, Wenkang Wang, Jinbo Liu, Yang Liu, Zhenqiang Sun, Junhong Hu.
      Tumor immunotherapy has transformed neoplastic disease management, yet low response rates and immune complications persist as major challenges. Extracellular vesicles including exosomes have emerged as therapeutic agents actively involved in a diverse range of pathological conditions. Mounting evidence suggests that alterations in the quantity and composition of extracellular vesicles (EVs) contribute to the remodeling of the immune-suppressive tumor microenvironment (TME), thereby influencing the efficacy of immunotherapy. This revelation has sparked clinical interest in utilizing EVs for immune sensitization. In this perspective article, we present a comprehensive overview of the origins, generation, and interplay among various components of EVs within the TME. Furthermore, we discuss the pivotal role of EVs in reshaping the TME during tumorigenesis and their specific cargo, such as PD-1 and non-coding RNA, which influence the phenotypes of critical immune cells within the TME. Additionally, we summarize the applications of EVs in different anti-tumor therapies, the latest advancements in engineering EVs for cancer immunotherapy, and the challenges encountered in clinical translation. In light of these findings, we advocate for a broader understanding of the impact of EVs on the TME, as this will unveil overlooked therapeutic vulnerabilities and potentially enhance the efficacy of existing cancer immunotherapies.
    Keywords:  Cancer immunotherapy; Engineered EVs; Extracellular vesicles; Lymph node microenvironment; Non-coding RNA; PD-1; Tumor microenvironment
    DOI:  https://doi.org/10.1186/s12943-023-01898-5
  18. Int J Mol Sci. 2023 Nov 25. pii: 16755. [Epub ahead of print]24(23):
    Cellular Responses to Extracellular Vesicles as Potential Markers of Colorectal Cancer Progression.
    Sonia Guarnerio, Robert Tempest, Rawan Maani, Stuart Hunt, Laura M Cole, Christine L Le Maitre, Keith Chapple, Nicholas Peake.
      The development of novel screening tests aims to support early asymptomatic diagnosis and subtyping patients according to similar traits in the heterogeneous cancer cohort. Extracellular vesicles (EVs) are promising candidates for the detection of disease markers from bodily fluids, but limitations in the standardisation of isolation methods and the intrinsic EV heterogeneity obtained from liquid biopsies are currently obstacles to clinical adoption. Here, cellular responses to cancer EVs were initially explored as potential complementary biomarkers for stage separation using colorectal cancer (CRC) SW480 and SW620 cell line models. A pilot study on a small cohort of CRC patients and controls was then developed by performing a multivariate analysis of cellular responses to plasma-derived EVs. Several cell activities and markers involved in tumour microenvironment pathways were influenced by the treatment of cell line EVs in a stage-dependent manner. The multivariate analysis combining plasma EV markers and cellular responses to plasma EVs was able to separate patients according to disease stage. This preliminary study offers the potential of considering cellular responses to EVs in combination with EV biomarkers in the development of screening methods.
    Keywords:  colorectal cancer; extracellular vesicles; responsive biomarkers
    DOI:  https://doi.org/10.3390/ijms242316755
  19. Cancer Gene Ther. 2023 Dec 11.
    Novel lncRNA Gm33149 modulates metastatic heterogeneity in melanoma by regulating the miR-5623-3p/Wnt axis via exosomal transfer.
    Yan Chen, Yu-Han Zhang, Jie Li, Lei Shi, Jia-Cheng Xie, Xue Han, Yu-Ting Chen, Meng Xiang, Bo-Wen Li, H Rosie Xing, Jian-Yu Wang.
      The high mortality rate associated with melanoma primarily results from metastasis and recurrence. However, the precise mechanisms driving these processes remain poorly understood. Intercellular communication between cancer cells and non-cancer cells significantly influences the tumor microenvironment and plays a crucial role in metastasis. Therefore, our current study aims to investigate the role and mechanism of long non-coding RNAs (lncRNAs) in regulating the interaction between melanoma cancer stem cells (CSCs) and non-CSCs during the metastatic colonization process. This study has characterized a novel lncRNA called Gm33149. Importantly, we provide evidence for the first time that Gm33149, originating from highly metastatic melanoma stem cells (OL-SD), can be packaged into exosomes and transferred to low-metastatic nonstem cells (OL). Once internalized by OL cells, Gm33149 exerts its function through a competitive endogenous RNA mechanism (ceRNA) involving miR-5623-3p. Specifically, Gm33149 competitively binds to miR-5623-3p, thereby activating the Wnt signaling pathway and promoting the acquisition of a more aggressive metastatic phenotype by OL cells. In summary, our findings suggest that targeting lncRNA Gm33149 within extracellular vesicles could potentially serve as a therapeutic strategy for the treatment of metastatic melanoma. Schematic representation of the mechanisms underlying the pro-metastatic activity of lncRNA Gm33149 mediated by exosomal transfer. The figure illustrates the key mechanisms involved in the pro-metastatic activity of lncRNA Gm33149 through exosomal transfer. Melanoma stem cells (OLSD) release exosomes containing lncRNA Gm33149. These exosomes are taken up by non-stem melanoma cells (OL), delivering lncRNA Gm33149 to the recipient cells. Within OL cells, lncRNA Gm33149 functions as a competitive endogenous RNA (ceRNA), sequestering miR-5623-3p. This sequestration prevents miR-5623-3p from binding to its target genes, thereby activating the Wnt signaling pathway. The activated Wnt signaling pathway enhances the migration, invasion, and metastatic colonization capabilities of OL cells. The transfer of lncRNA Gm33149 via exosomes contributes to OL cells acquiring "metastatic competency" while promoting their metastatic colonization. These findings underscore the importance of lncRNA Gm33149 in intercellular communication and the metastatic progression of melanoma.
    DOI:  https://doi.org/10.1038/s41417-023-00707-x
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