bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2023–07–02
sixteen papers selected by
Muhammad Rizwan, COMSATS University
  1. Exosomal circRNA: emerging insights into cancer progression and clinical application potential.
  2. Exosomes as Novel Diagnostic Biomarkers and Therapeutic Tools in Gliomas.
  3. [Expression and Clinical Significance of Exosome Derived MiR-181b-5p in Children with Acute Lymphoblastic Leukemia].
  4. Exosomes Derived from Colon Cancer Cells Promote Tumor Progression and Affect the Tumor Microenvironment.
  5. Milk Exosomes: Next-Generation Agents for Delivery of Anticancer Drugs and Therapeutic Nucleic Acids.
  6. Blood-Derived Exosomal hTERT mRNA in Patients with Lung Cancer: Characterization and Correlation with Response to Therapy.
  7. Potential Avenues for Exosomal Isolation and Detection Methods to Enhance Small-Cell Lung Cancer Analysis.
  8. Neutrophils in Cancer and Potential Therapeutic Strategies Using Neutrophil-Derived Exosomes.
  9. M2 Macrophages-Derived Exosomal miRNA-23a-3p Promotes the Progression of Oral Squamous Cell Carcinoma by Targeting PTEN.
  10. The therapeutic potential of exosomes in lung cancer.
  11. Horizontal Transfer of Malignant Traits and the Involvement of Extracellular Vesicles in Metastasis.
  12. Role of Pancreatic Tumour-Derived Exosomes and Their Cargo in Pancreatic Cancer-Related Diabetes.
  13. Serum extracellular vesicles derived hsa-miR-320d as an indicator for progression of clear cell renal cell carcinoma.
  14. Extracellular vesicles in tumorigenesis, metastasis, chemotherapy resistance and intercellular communication in osteosarcoma.
  15. Stromal cell-derived small extracellular vesicles enhance radioresistance of prostate cancer cells via interleukin-8-induced autophagy.
  16. Diagnostic performance of serum exosomal miRNA-720 in hepatocellular carcinoma.
  1. J Hematol Oncol. 2023 06 26. 16(1): 67
    Exosomal circRNA: emerging insights into cancer progression and clinical application potential.
    Fan Zhang, Jiajia Jiang, Hui Qian, Yongmin Yan, Wenrong Xu.
      Exosomal circRNA serves a novel genetic information molecule, facilitating communication between tumor cells and microenvironmental cells, such as immune cells, fibroblasts, and other components, thereby regulating critical aspects of cancer progression including immune escape, tumor angiogenesis, metabolism, drug resistance, proliferation and metastasis. Interestingly, microenvironment cells have new findings in influencing tumor progression and immune escape mediated by the release of exosomal circRNA. Given the intrinsic stability, abundance, and broad distribution of exosomal circRNAs, they represent excellent diagnostic and prognostic biomarkers for liquid biopsy. Moreover, artificially synthesized circRNAs may open up new possibilities for cancer therapy, potentially bolstered by nanoparticles or plant exosome delivery strategies. In this review, we summarize the functions and underlying mechanisms of tumor cell and non-tumor cell-derived exosomal circRNAs in cancer progression, with a special focus on their roles in tumor immunity and metabolism. Finally, we examine the potential application of exosomal circRNAs as diagnostic biomarkers and therapeutic targets, highlighting their promise for clinical use.
    Keywords:  Biomarker; Cancer therapy; Exosome; Tumor immunity; Tumor metabolism; circRNA
    DOI:  https://doi.org/10.1186/s13045-023-01452-2
  2. Int J Mol Sci. 2023 Jun 15. pii: 10162. [Epub ahead of print]24(12):
    Exosomes as Novel Diagnostic Biomarkers and Therapeutic Tools in Gliomas.
    Panagiotis Skouras, Antonios N Gargalionis, Christina Piperi.
      Exosomes constitute small extracellular vesicles that contain lipids, proteins, nucleic acids, and glycoconjugates from the secreted cells and are capable of transmitting signals between cells and coordinating cellular communication. By this means, they are ultimately involved in physiology and disease, including development, homeostasis, and immune system regulation, as well as contributing to tumor progression and neurodegenerative diseases pathology. Recent studies have shown that gliomas secrete a panel of exosomes which have been associated with cell invasion and migration, tumor immune tolerance, potential for malignant transformation, neovascularization, and resistance to treatment. Exosomes have therefore emerged as intercellular communicators, which mediate the tumor-microenvironment interactions and exosome-regulated glioma cell stemness and angiogenesis. They may induce tumor proliferation and malignancy in normal cells by carrying pro-migratory modulators from cancer cells as well as many different molecular cancer modifiers, such as oncogenic transcripts, miRNAs, mutant oncoproteins, etc., which promote the communication of cancer cells with the surrounding stromal cells and provide valuable information on the molecular profile of the existing tumor. Moreover, engineered exosomes can provide an alternative system for drug delivery and enable efficient treatment. In the present review, we discuss the latest findings regarding the role of exosomes in glioma pathogenesis, their utility in non-invasive diagnosis, and potential applications to treatment.
    Keywords:  brain tumors; drug delivery; exosome; extracellular vesicles; glioblastoma; glioma
    DOI:  https://doi.org/10.3390/ijms241210162
  3. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Jun;31(3): 643-648
    [Expression and Clinical Significance of Exosome Derived MiR-181b-5p in Children with Acute Lymphoblastic Leukemia].
    Yi Hong, Kang-Kang Liu, Ning-Ling Wang, Zhi-Wei Xie, Jin-Hua Chu.
       OBJECTIVE: To explore the expression level of exosome derived miR-181b-5p in different disease stages of children with acute lymphoblastic leukemia and its relationship with clinical characteristics.
    METHODS: Bone marrow plasma samples of 86 children with ALL were collected. Exosomes were extracted by exosome extraction kit, and RNA in exosomes was extracted by TRIzol method. The levels of miR-181b-5p in the blood plasma exosomes of the patients in the newly diagnosed group, relapse group, remission group and control group were detected by qRT- PCR. The difference of miR-181b-5p expression level in each group was compared and analyzed, and the relationship between miR-181b-5p expression level and clinical characteristics was analyzed.
    RESULTS: The expression level of exosomal miR-181b-5p in the newly diagnosed group and the relapsed group was significantly lower than that in the remission group and the control group (P< 0.05). The expression level of exosomal miR-181b-5p in T-ALL children was higher than that in B-ALL children (P<0.05). The expression level of plasma exosomal miR-181b-5p in male children was higher than that in female children (P<0.01).
    CONCLUSION: Exosome derived miR-181b-5p changes dynamically in the course of ALL children, and can be used as a marker miRNA to monitor disease status. Exosomes can transmit information in the tumor microenvironment and serve as a potential carrier for biomolecular targeted therapy.
    Keywords:  acute lymphoblastic leukemia ; children ; clinical characteristics ; exosomes ; miR-181b-5p
    DOI:  https://doi.org/10.19746/j.cnki.issn.1009-2137.2023.03.004
  4. J Clin Med. 2023 Jun 07. pii: 3905. [Epub ahead of print]12(12):
    Exosomes Derived from Colon Cancer Cells Promote Tumor Progression and Affect the Tumor Microenvironment.
    Minsung Kim, Il Tae Son, Gyoung Tae Noh, So-Youn Woo, Ryung-Ah Lee, Bo Young Oh.
      Cancer-cell-derived exosomes confer oncogenic properties in their tumor microenvironment and to other cells; however, the exact mechanism underlying this process is unclear. Here, we investigated the roles of cancer-cell-derived exosomes in colon cancer. Exosomes were isolated from colon cancer cell lines, HT-29, SW480, and LoVo, using an ExoQuick-TC kit, identified using Western blotting for exosome markers, and characterized using transmission electron microscopy and nanosight tracking analysis. The isolated exosomes were used to treat HT-29 to evaluate their effect on cancer progression, specifically cell viability and migration. Cancer-associated fibroblasts (CAFs) were obtained from patients with colorectal cancer to analyze the effect of the exosomes on the tumor microenvironment. RNA sequencing was performed to evaluate the effect of the exosomes on the mRNA component of CAFs. The results showed that exosome treatment significantly increased cancer cell proliferation, upregulated N-cadherin, and downregulated E-cadherin. Exosome-treated cells exhibited higher motility than control cells. Compared with control CAFs, exosome-treated CAFs showed more downregulated genes. The exosomes also altered the regulation of different genes involved in CAFs. In conclusion, colon cancer-cell-derived exosomes affect cancer cell proliferation and the epithelial-mesenchymal transition. They promote tumor progression and metastasis and affect the tumor microenvironment.
    Keywords:  exosomes; mRNA; microRNA; tumor microenvironment; tumor progression
    DOI:  https://doi.org/10.3390/jcm12123905
  5. Int J Mol Sci. 2023 Jun 15. pii: 10194. [Epub ahead of print]24(12):
    Milk Exosomes: Next-Generation Agents for Delivery of Anticancer Drugs and Therapeutic Nucleic Acids.
    Anna M Timofeeva, Anastasia P Paramonik, Sergey S Sedykh, Georgy A Nevinsky.
      Exosomes are nanovesicles 40-120 nm in diameter secreted by almost all cell types and providing humoral intercellular interactions. Given the natural origin and high biocompatibility, the potential for loading various anticancer molecules and therapeutic nucleic acids inside, and the surface modification possibility for targeted delivery, exosomes are considered to be a promising means of delivery to cell cultures and experimental animal organisms. Milk is a unique natural source of exosomes available in semi-preparative and preparative quantities. Milk exosomes are highly resistant to the harsh conditions of the gastrointestinal tract. In vitro studies have demonstrated that milk exosomes have an affinity to epithelial cells, are digested by cells by endocytosis mechanism, and can be used for oral delivery. With milk exosome membranes containing hydrophilic and hydrophobic components, exosomes can be loaded with hydrophilic and lipophilic drugs. This review covers a number of scalable protocols for isolating and purifying exosomes from human, cow, and horse milk. Additionally, it considers passive and active methods for drug loading into exosomes, as well as methods for modifying and functionalizing the surface of milk exosomes with specific molecules for more efficient and specific delivery to target cells. In addition, the review considers various approaches to visualize exosomes and determine cellular localization and bio-distribution of loaded drug molecules in tissues. In conclusion, we outline new challenges for studying milk exosomes, a new generation of targeted delivery agents.
    Keywords:  cargo loading; drug delivery; exosomes; extracellular vesicles; milk exosomes; milk vesicles; target delivery; visualization
    DOI:  https://doi.org/10.3390/ijms241210194
  6. Biomedicines. 2023 Jun 16. pii: 1730. [Epub ahead of print]11(6):
    Blood-Derived Exosomal hTERT mRNA in Patients with Lung Cancer: Characterization and Correlation with Response to Therapy.
    Ofer Rotem, Alona Zer, Lilach Yosef, Einat Beery, Hadar Goldvaser, Anna Gutkin, Ron Levin, Elizabeth Dudnik, Tamar Berger, Meora Feinmesser, Adva Levy-Barda, Meir Lahav, Pia Raanani, Orit Uziel.
      Background: Telomerase (human telomerase reverse transcriptase (hTERT) is considered a hallmark of cancer, being active in cancer cells but repressed in human somatic cells. As such, it has the potential to serve as a valid cancer biomarker. Exosomal hTERT mRNA can be detected in the serum of patients with solid malignancies but not in healthy individuals. We sought to evaluate the feasibility of measuring serum exosomal hTERT transcripts levels in patients with lung cancer. Methods: A prospective analysis of exosomal hTERT mRNA levels was determined in serum-derived exosomes from 76 patients with stage III-IV lung cancer (11 SCLC and 65 NSCLC). An hTERT level above RQ = 1.2 was considered "detectable" according to a previous receiver operating characteristic curve (ROC) curve. Sequential measurements were obtained in 33 patients. Demographic and clinical data were collected retrospectively from patients' charts. Data on response to systemic therapy (chemotherapy, immunotherapy, and tyrosine kinase inhibitors) were collected by the treating physicians. Results: hTERT was detected in 53% (40/76) of patients with lung cancer (89% of SCLC and 46% of NSLCC). The mean hTERT levels were 3.7 in all 76 patients, 5.87 in SCLC patients, and 3.62 in NSCLC patients. In total, 25 of 43 patients with sequential measurements had detectable levels of hTERT. The sequential exosomal hTERT mRNA levels reflected the clinical course in 23 of them. Decreases in hTERT levels were detected in 17 and 5 patients with partial and complete response, respectively. Eleven patients with a progressive disease had an increase in the level of exosomal hTERT, and seven with stable disease presented increases in its exosomal levels. Another patient who progressed on the first line of treatment and had a partial response to the second line of treatment exhibited an increase in exosomal hTERT mRNA levels during the progression and a decrease during the response. Conclusions: Exosomal hTERT mRNA levels are elevated in over half of patients with lung cancer. The potential association between hTERT levels and response to therapy suggests its utility as a promising cancer biomarker for response to therapy. This issue should be further explored in future studies.
    Keywords:  exosomes; hTERT; non-small-cell lung carcinoma (NSCLC); small-cell lung carcinoma (SCLC)
    DOI:  https://doi.org/10.3390/biomedicines11061730
  7. ACS Meas Sci Au. 2023 Jun 21. 3(3): 143-161
    Potential Avenues for Exosomal Isolation and Detection Methods to Enhance Small-Cell Lung Cancer Analysis.
    Waqar Ahmed Afridi, Simon Strachan, Surasak Kasetsirikul, Amandeep Singh Pannu, Narshone Soda, Daniel Gough, Nam-Trung Nguyen, Muhammad J A Shiddiky.
      Around the world, lung cancer has long been the main factor in cancer-related deaths, with small-cell lung cancer (SCLC) being the deadliest form of lung cancer. Cancer cell-derived exosomes and exosomal miRNAs are considered promising biomarkers for diagnosing and prognosis of various diseases, including SCLC. Due to the rapidity of SCLC metastasis, early detection and diagnosis can offer better diagnosis and prognosis and therefore increase the patient's chances of survival. Over the past several years, many methodologies have been developed for analyzing non-SCLC-derived exosomes. However, minimal advances have been made in SCLC-derived exosome analysis methodologies. This Review discusses the epidemiology and prominent biomarkers of SCLC. Followed by a discussion about the effective strategies for isolating and detecting SCLC-derived exosomes and exosomal miRNA, highlighting the critical challenges and limitations of current methodologies. Finally, an overview is provided detailing future perspectives for exosome-based SCLC research.
    DOI:  https://doi.org/10.1021/acsmeasuresciau.2c00068
  8. Vaccines (Basel). 2023 May 26. pii: 1028. [Epub ahead of print]11(6):
    Neutrophils in Cancer and Potential Therapeutic Strategies Using Neutrophil-Derived Exosomes.
    Abhishek Dutta, Shrikrishna Bhagat, Swastika Paul, Jonathan P Katz, Debomita Sengupta, Dharmendra Bhargava.
      Neutrophils are the most abundant immune cells and make up about 70% of white blood cells in human blood and play a critical role as the first line of defense in the innate immune response. They also help regulate the inflammatory environment to promote tissue repair. However, in cancer, neutrophils can be manipulated by tumors to either promote or hinder tumor growth depending on the cytokine pool. Studies have shown that tumor-bearing mice have increased levels of neutrophils in peripheral circulation and that neutrophil-derived exosomes can deliver various cargos, including lncRNA and miRNA, which contribute to tumor growth and degradation of extracellular matrix. Exosomes derived from immune cells generally possess anti-tumor activities and induce tumor-cell apoptosis by delivering cytotoxic proteins, ROS generation, H2O2 or activation of Fas-mediated apoptosis in target cells. Engineered exosome-like nanovesicles have been developed to deliver chemotherapeutic drugs precisely to tumor cells. However, tumor-derived exosomes can aggravate cancer-associated thrombosis through the formation of neutrophil extracellular traps. Despite the advancements in neutrophil-related research, a detailed understanding of tumor-neutrophil crosstalk is still lacking and remains a major barrier in developing neutrophil-based or targeted therapy. This review will focus on the communication pathways between tumors and neutrophils, and the role of neutrophil-derived exosomes (NDEs) in tumor growth. Additionally, potential strategies to manipulate NDEs for therapeutic purposes will be discussed.
    Keywords:  ADCC and ADCP; Neutrophils; immune suppression; metastasis; neutrophil-derived exosomes; neutrophil-extracellular trap; trogocytosis; tumor microenvironment; tumor-associated neutrophils
    DOI:  https://doi.org/10.3390/vaccines11061028
  9. Curr Issues Mol Biol. 2023 Jun 07. 45(6): 4936-4947
    M2 Macrophages-Derived Exosomal miRNA-23a-3p Promotes the Progression of Oral Squamous Cell Carcinoma by Targeting PTEN.
    Jun Li, Yongjie Bao, Sisi Peng, Chao Jiang, Luying Zhu, Sihai Zou, Jie Xu, Yong Li.
      Exosomes from tumor cells and immune cells regulate the tumor microenvironment through the biomolecules or microRNAs (miRNAs) they carry. This research aims to investigate the role of miRNA in exosomes derived from tumor-associated macrophages (TAMs) in the progression of oral squamous cell carcinoma (OSCC). RT-qPCR and Western blotting assays were used to determine the expression of genes and proteins in OSCC cells. CCK-8, Scratch assay and invasion-related proteins were utilized to detect the malignant progression of tumor cells. High-throughput sequencing predicted differentially expressed miRNAs in exosomes secreted by M0 and M2 macrophages. Compared with exosomes from M0 macrophages, exosomes from M2 macrophages led to enhanced proliferation and invasion of OSCC cells and inhibited their apoptosis. High-throughput sequencing results show that miR-23a-3p is differentially expressed in exosomes from M0 and M2 macrophages. MiRNA target gene database predicts that phosphatase and tensin homolog (PTEN) are target genes of miR-23a-3p. Further studies revealed that transfection of miR-23a-3p mimics inhibited PTEN expression in vivo and in vitro and promoted the malignant progression of OSCC cells, which was reversed by miR-23a-3p inhibitors. MiR-23a-3p in exosomes derived from M2 macrophages promotes malignant progression of OSCC. PTEN is a potential intracellular target of miR-23a-3p. MiR-23a-3p, an M2 macrophage-associated exosome, is a promising target for the future treatment of OSCC.
    Keywords:  M2 macrophages; MiR-23a-3p; OSCC; PTEN; exosome
    DOI:  https://doi.org/10.3390/cimb45060314
  10. Cell Oncol (Dordr). 2023 May 11.
    The therapeutic potential of exosomes in lung cancer.
    Hongyuan Liang, Lingyun Zhang, Xiangxuan Zhao, Jian Rong.
       BACKGROUND: Lung cancer (LC) is one of the most common malignancies globally. Besides early detection and surgical resection, there is currently no effective curative treatment for metastatic advanced LC. Exosomes are endogenous nano-extracellular vesicles produced by somatic cells that play an important role in the development and maintenance of normal physiology. Exosomes can carry proteins, peptides, lipids, nucleic acids, and various small molecules for intra- and intercellular material transport or signal transduction. LC cells can maintain their survival, proliferation, migration, invasion, and metastasis, by producing or interacting with exosomes. Basic and clinical data also show that exosomes can be used to suppress LC cell proliferation and viability, induce apoptosis, and enhance treatment sensitivity. Due to the high stability and target specificity, good biocompatibility, and low immunogenicity of exosomes, they show promise as vehicles of LC therapy.
    CONCLUSION: We have written this comprehensive review to communicate the LC treatment potential of exosomes and their underlying molecular mechanisms. We found that overall, LC cells can exchange substances or crosstalk with themselves or various other cells in the surrounding TME or distant organs through exosomes. Through this, they can modulate their survival, proliferation, stemness, migration, and invasion, EMT, metastasis, and apoptotic resistance.
    Keywords:  Chemotherapy; Exosome; Lung cancer; Prognosis; Target therapy
    DOI:  https://doi.org/10.1007/s13402-023-00815-8
  11. Cells. 2023 06 06. pii: 1566. [Epub ahead of print]12(12):
    Horizontal Transfer of Malignant Traits and the Involvement of Extracellular Vesicles in Metastasis.
    Goffredo O Arena, Stefano Forte, Mohamed Abdouh, Cheryl Vanier, Denis Corbeil, Aurelio Lorico.
      Metastases are responsible for the vast majority of cancer deaths, yet most therapeutic efforts have focused on targeting and interrupting tumor growth rather than impairing the metastatic process. Traditionally, cancer metastasis is attributed to the dissemination of neoplastic cells from the primary tumor to distant organs through blood and lymphatic circulation. A thorough understanding of the metastatic process is essential to develop new therapeutic strategies that improve cancer survival. Since Paget's original description of the "Seed and Soil" hypothesis over a hundred years ago, alternative theories and new players have been proposed. In particular, the role of extracellular vesicles (EVs) released by cancer cells and their uptake by neighboring cells or at distinct anatomical sites has been explored. Here, we will outline and discuss these alternative theories and emphasize the horizontal transfer of EV-associated biomolecules as a possibly major event leading to cell transformation and the induction of metastases. We will also highlight the recently discovered intracellular pathway used by EVs to deliver their cargoes into the nucleus of recipient cells, which is a potential target for novel anti-metastatic strategies.
    Keywords:  cancer; exosomes; extracellular vesicles; metastasis; microenvironment; nucleoplasmic reticulum; oncogene; tumor suppressor gene
    DOI:  https://doi.org/10.3390/cells12121566
  12. Int J Mol Sci. 2023 Jun 15. pii: 10203. [Epub ahead of print]24(12):
    Role of Pancreatic Tumour-Derived Exosomes and Their Cargo in Pancreatic Cancer-Related Diabetes.
    Helen B Binang, Chamini J Perera, Minoti V Apte.
      One of the most common and deadly types of pancreatic cancer (PC) is pancreatic ductal adenocarcinoma (PDAC), with most patients succumbing to the disease within one year of diagnosis. Current detection strategies do not address asymptomatic PC; therefore, patients are diagnosed at an advanced stage when curative treatment is often no longer possible. In order to detect PC in asymptomatic patients earlier, the risk factors that could serve as reliable markers need to be examined. Diabetic mellitus (DM) is a significant risk factor for this malignancy and can be both a cause and consequence of PC. Typically, DM caused by PC is known as new-onset, pancreatogenic, pancreoprivic, or pancreatic cancer-related diabetes (PCRD). Although PCRD is quite distinct from type 2 DM (T2DM), there are currently no biomarkers that differentiate PCRD from T2DM. To identify such biomarkers, a better understanding of the mechanisms mediating PCRD is essential. To this end, there has been a growing research interest in recent years to elucidate the role of tumour-derived exosomes and their cargo in the pathogenesis of PCRD. Exosomes derived from tumours can be recognized for their specificity because they reflect the characteristics of their parent cells and are important in intercellular communication. Their cargo consists of proteins, lipids, and nucleic acids, which can be transferred to and alter the behaviour of recipient cells. This review provides a concise overview of current knowledge regarding tumour-derived exosomes and their cargo in PCRD and discusses the potential areas worthy of further study.
    Keywords:  biomarkers; exosomes; pancreatic adenocarcinoma; pancreatic cancer; pancreatic cancer-related diabetes
    DOI:  https://doi.org/10.3390/ijms241210203
  13. Discov Oncol. 2023 Jun 28. 14(1): 114
    Serum extracellular vesicles derived hsa-miR-320d as an indicator for progression of clear cell renal cell carcinoma.
    Yizheng Xue, Tianyi Chen, Naiqiao Hou, Xiaorong Wu, Wen Kong, Jiwei Huang, Jin Zhang, Yonghui Chen, Junhua Zheng, Wei Zhai, Wei Xue.
       BACKGROUND: Renal cell carcinoma (RCC) is a prevalent malignancy with a rising incidence in developing countries. Clear cell renal cell carcinoma (ccRCC) constitutes 70% of RCC cases and is prone to metastasis and recurrence, yet lacks a liquid biomarker for surveillance. Extracellular vesicles (EVs) have shown promise as biomarkers in various malignancies. In this study, we investigated the potential of serum EV-derived miRNAs as a biomarker for ccRCC metastasis and recurrence.
    MATERIALS AND METHODS: Patients diagnosed with ccRCC between 2017 and 2020 were recruited in this study. In the discovery phase, high throughput small RNA sequencing was used to analyze RNA extracted from serum EVs derived from localized ccRCC (LccRCC) and advanced ccRCC (AccRCC). In the validation phase, qPCR was employed for quantitative detection of candidate biomarkers. Migration and invasion assays were performed on ccRCC cell line OSRC2.
    RESULTS: Serum EVs derived hsa-miR-320d was significantly up-regulated in patients with AccRCC than in patients with LccRCC (p < 0.01). In addition, Serum EVs derived hsa-miR-320d was also significantly up-regulated in patients who experienced recurrence or metastasis (p < 0.01). Besides, hsa-miR-320d enhances the pro-metastatic phenotype of ccRCC cells in vitro.
    CONCLUSIONS: Serum EVs derived hsa-miR-320d as a liquid biomarker exhibits significant potential for identifying the recurrence or metastasis of ccRCC, as well as hsa-miR-320d promotes ccRCC cells migration and invasion.
    Keywords:  Biomarker; Clear cell renal cell carcinoma; Extracellular vesicles; Hsa-miR-320d
    DOI:  https://doi.org/10.1007/s12672-023-00730-2
  14. Bioengineered. 2023 12;14(1): 113-128
    Extracellular vesicles in tumorigenesis, metastasis, chemotherapy resistance and intercellular communication in osteosarcoma.
    Yi Liao, Qian Yi, Jinglong He, Dixi Huang, Jianyi Xiong, Wei Sun, Weichao Sun.
       HIGHLIGHTS: Extracellular vehicles play crucial function in osteosarcoma tumorigenesis.Extracellular vehicles mediated the intercellular communication of osteosarcoma cells with other types cells in tumor microenvironment.Extracellular vehicles have potential utility in osteosarcoma diagnosis and treatment.
    Keywords:  Osteosarcoma; drug resistance; extracellular vesicles; metastasis; therapeutics; tumor microenvironment
    DOI:  https://doi.org/10.1080/21655979.2022.2161711
  15. J Extracell Vesicles. 2023 Jul;12(7): e12342
    Stromal cell-derived small extracellular vesicles enhance radioresistance of prostate cancer cells via interleukin-8-induced autophagy.
    Xiumei Wang, Fan Xu, Hengyuan Kou, Yawen Zheng, Jing Yang, Zhi Xu, Yao Fang, Wenbo Sun, Shuyi Zhu, Qin Jiang, Xiaowei Wei, Yong Xu.
      Radiation is a curative treatment for localized prostate cancer (PCa). Unfortunately, radiotherapeutic efficacy is often diminished when patients develop more aggressive or metastatic phenotypes. Recent studies have demonstrated that extracellular vesicles participate in cancer therapeutic resistance by delivering small bioactive molecules, such as small non-coding RNAs. Here, we show that stromal cell-derived small extracellular vesicles (sEVs) facilitate the radioresistance of PCa cells by transporting interleukin-8 (IL-8). Indeed, prostatic stromal cells secrete more IL-8 than AR-positive PCa cells, which can be accumulated in sEVs. Intriguingly, the uptake of stromal cells-derived sEVs by radiosensitive PCa cells enhanced their radioresistance, which could be attenuated by silencing CXCL8 in stromal cells or inhibiting its receptor CXCR2 in PCa cells. sEV-mediated radioresistance has been validated in zebrafish and mouse xenograft tumours. Mechanistically, the uptake of stromal sEVs triggers the AMPK-activated autophagy pathway in PCa cells under the irradiation condition. Consequently, inactivating AMPK efficiently resensitized radiotherapy either by utilizing an AMPK inhibitor or silencing AMPKα in PCa cells. Furthermore, chloroquine (CQ), a lysosomal inhibitor, sufficiently resensitized radiotherapy via blockade of autophagolysosome fusion, leading to autophagosome accumulation in PC cells. Collectively, these results suggest that stromal cells enhance the radioresistance of PCa cells mainly through sEVs that deliver IL-8.
    Keywords:  AMPK; autophagy; chloroquine; interleukin-8; prostate cancer; radioresistance; small extracellular vesicles; stromal cells
    DOI:  https://doi.org/10.1002/jev2.12342
  16. J Liver Cancer. 2022 Mar;22(1): 30-39
    Diagnostic performance of serum exosomal miRNA-720 in hepatocellular carcinoma.
    Jeong Won Jang, Ji Min Kim, Hye Seon Kim, Jin Seoub Kim, Ji Won Han, Soon Kyu Lee, Heechul Nam, Pil Soo Sung, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon.
       Background/Aim: Hepatocellular carcinoma (HCC) is associated with poor prognosis, largely due to late detection. Highly accurate biomarkers are urgently needed to detect early-stage HCC. Our study aims to explore the diagnostic performance of serum exosomal microRNA (miR)-720 in HCC.
    Methods: Exosomal miRNA was measured via quantitative real-time PCR. A correlation analysis of exosomal miR-720 and tumor or clinico-demographic data of patients with HCC was performed. The receiver operating characteristic (ROC) curve was used to assess the diagnostic capacity of serum exosomal miR-720 for HCC, in comparison with α-fetoprotein (AFP) and prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II).
    Results: MiR-720 was chosen as a potential HCC marker via miR microarray based on significant differential expression between tumor and non-tumor samples. Serum exosomal miR-720 was significantly upregulated in patients with HCC (n=114) versus other liver diseases (control, n=30), with a higher area under the ROC curve (AUC, 0.931) than the other markers. Particularly, serum exosomal miR-720 showed superior performance in diagnosing small HCC (<5 cm; AUC, 0.930) compared with AFP (AUC, 0.802) or PIVKA-II (AUC, 0.718). Exosomal miR-720 levels showed marginal correlation with tumor size. The proportion of elevated miR-720 also increased with intrahepatic tumor stage progression. Unlike AFP or PIVKA-II showing a significant correlation with aminotransferase levels, the exosomal miR-720 level was not affected by aminotransferase levels.
    Conclusions: Serum exosomal miR-720 is an excellent biomarker for the diagnosis of HCC, with better performance than AFP or PIVKA-II. Its diagnostic utility is maintained even in small HCC and is unaffected by aminotransferase levels.
    Keywords:  Biomarkers; Diagnosis; Exosome; Hepatocellular carcinoma; MicroRNA
    DOI:  https://doi.org/10.17998/jlc.2022.02.25
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