bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2023–01–15
fiveteen papers selected by
Muhammad Rizwan, COMSATS University
  1. Drug Resistance: The Role of Exosomal miRNA in the Microenvironment of Hematopoietic Tumors.
  2. Role of tumor-derived exosomes in metastasis, drug resistance and diagnosis of clear cell renal cell carcinoma.
  3. Decoding Roles of Exosomal lncRNAs in Tumor-Immune Regulation and Therapeutic Potential.
  4. [Exosomal miR-10b Promotes Invasion and Epithelial-mesenchymal Transformation of Lung Adenocarcinoma A549 Cells by Regulating Macrophage M2 Polarization].
  5. Comparative Analysis of Tumor-Associated microRNAs and Tetraspanines from Exosomes of Plasma and Ascitic Fluids of Ovarian Cancer Patients.
  6. Advanced technologies for molecular diagnosis of cancer: State of pre-clinical tumor-derived exosome liquid biopsies.
  7. Serum-Exosome-Derived miRNAs Serve as Promising Biomarkers for HCC Diagnosis.
  8. Exosomal miR-10527-5p Inhibits Migration, Invasion, Lymphangiogenesis and Lymphatic Metastasis by Affecting Wnt/β-Catenin Signaling via Rab10 in Esophageal Squamous Cell Carcinoma.
  9. Tumor-Derived Extracellular Vesicles in Cancer Immunoediting and Their Potential as Oncoimmunotherapeutics.
  10. Tumor Cell-Derived Exosomal circ-PRKCI Promotes Proliferation of Renal Cell Carcinoma via Regulating miR-545-3p/CCND1 Axis.
  11. Exosome-Based Smart Drug Delivery Tool for Cancer Theranostics.
  12. An exosome-based liquid biopsy signature for pre-operative identification of lymph node metastasis in patients with pathological high-risk T1 colorectal cancer.
  13. MiRNAs from serum-derived extracellular vesicles as biomarkers for uveal melanoma progression.
  14. Exosome-Derived microRNA: Implications in Melanoma Progression, Diagnosis and Treatment.
  15. Combination of Small Extracellular Vesicle-Derived Annexin A2 Protein and mRNA as a Potential Predictive Biomarker for Chemotherapy Responsiveness in Aggressive Triple-Negative Breast Cancer.
  1. Molecules. 2022 Dec 23. pii: 116. [Epub ahead of print]28(1):
    Drug Resistance: The Role of Exosomal miRNA in the Microenvironment of Hematopoietic Tumors.
    Mariaconcetta Cariello, Angela Squilla, Martina Piacente, Giorgia Venutolo, Alessio Fasano.
      Extracellular vesicles (EVs), including exosomes, have an important role thanks to their ability to communicate and exchange information between tumor cells and the tumor microenvironment (TME), and have also been associated with communicating anti-cancer drug resistance (DR). The increase in proliferation of cancer cells alters oxygen levels, which causes hypoxia and results in a release of exosomes by the cancer cells. In this review, the results of studies examining the role of exosomal miRNA in DR, and their mechanism, are discussed in detail in hematological tumors: leukemia, lymphoma, and multiple myeloma. In conclusion, we underline the exosome's function as a possible drug delivery vehicle by understanding its cargo. Engineered exosomes can be used to be more specific for personalized therapy.
    Keywords:  drug resistance; exosomes; hypoxia; miRNAs; tumor microenvironment
    DOI:  https://doi.org/10.3390/molecules28010116
  2. Front Oncol. 2022 ;12 1066288
    Role of tumor-derived exosomes in metastasis, drug resistance and diagnosis of clear cell renal cell carcinoma.
    Tiancheng Jiang, Zepeng Zhu, Jiawei Zhang, Ming Chen, Shuqiu Chen.
      Renal cancer is one of the most extensively studied human tumors today, with clear cell renal cell carcinoma accounting for approximately 80% of all cases. Despite recent advances in research on clear cell renal cell carcinoma, advanced distant metastasis of the disease, delay in diagnosis, as well as drug resistance remain major problems. In recent years, as an important mediator of material and information exchange between cells in the tumor microenvironment, exosomes have attracted widespread attention for their role in tumor development. It has been reported that tumor-derived exosomes may act as regulators and have an important effect on the metastasis, drug resistance formation, and providing targets for early diagnosis of clear cell renal cell carcinoma. Therefore, the extensive study of tumour-derived exosomes will provide a meaningful reference for the development of the diagnostic and therapeutic field of clear cell renal cell carcinoma. This article reviews the biological role and research progress of tumor-derived exosomes in different aspects of premetastatic niche formation, tumor angiogenesis, and epithelial-mesenchymal transition during the progression of clear cell renal cell carcinoma. In addition, the role of tumor-derived exosomes in the development of drug resistance in clear cell renal cell carcinoma is also addressed in this review. Furthermore, recent studies have found that cargoes of exosomes in serum and urine, for example, a series of miRNAs, have the potential to be biological markers of clear cell renal cell carcinoma and provide meaningful targets for early diagnosis and monitoring of tumors, which is also covered in this article.
    Keywords:  clear cell renal cell carcinoma; diagnosis; drug resistance; metastasis; tumor-derived exosomes
    DOI:  https://doi.org/10.3389/fonc.2022.1066288
  3. Cancers (Basel). 2022 Dec 31. pii: 286. [Epub ahead of print]15(1):
    Decoding Roles of Exosomal lncRNAs in Tumor-Immune Regulation and Therapeutic Potential.
    Wenqin Zhang, Yuanliang Yan, Jinwu Peng, Abhimanyu Thakur, Ning Bai, Keda Yang, Zhijie Xu.
      Exosomes are nanovesicles secreted into biofluids by various cell types and have been implicated in different physiological and pathological processes. Interestingly, a plethora of studies emphasized the mediating role of exosomes in the bidirectional communication between donor and recipient cells. Among the various cargoes of exosomes, long non-coding RNAs (lncRNAs) have been identified as crucial regulators between cancer cells and immune cells in the tumor microenvironment (TME) that can interfere with innate and adaptive immune responses to affect the therapeutic efficiency. Recently, a few major studies have focused on the exosomal lncRNA-mediated interaction between cancer cells and immune cells infiltrated into TME. Nevertheless, a dearth of studies pertains to the immune regulating role of exosomal lncRNAs in cancer and is still in the early stages. Comprehensive mechanisms of exosomal lncRNAs in tumor immunity are not well understood. Herein, we provide an overview of the immunomodulatory function of exosomal lncRNAs in cancer and treatment resistance. In addition, we also summarize the potential therapeutic strategies toward exosomal lncRNAs in TME.
    Keywords:  cancer; exosomes; immunoregulation; immunotherapy; lncRNA
    DOI:  https://doi.org/10.3390/cancers15010286
  4. Zhongguo Fei Ai Za Zhi. 2022 Dec 20. 25(12): 835-842
    [Exosomal miR-10b Promotes Invasion and Epithelial-mesenchymal Transformation of Lung Adenocarcinoma A549 Cells by Regulating Macrophage M2 Polarization].
    Yan Yuan, Limin Guo, Shan Guo.
       BACKGROUND: Metastasis is the main cause of death in patients with lung cancer. Macrophages are innate immune cells that play important roles in cancer metastasis. Exosomes could play an important role of communication between tumor cells and macrophages. This study investigated the effect of miR-10b on cell growth invasion and epithelial mesenchymal transition (EMT) in lung adenocarcinoma A549 cell exosomes.
    METHODS: Exosomes were isolated from A549 cells and identified by transmission electron microscopy (TEM) and Western blot. CCK-8 assay and flow cytometry were used to detect cell proliferation and apoptosis. Cell migration and invasion were detected by Transwell assay. The expression of mRNA and protein were assessed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot, respectively.
    RESULTS: The expression of miR-10b was up-regulated in non-small cell lung cancer, and miR-10b inhibitor could inhibit the proliferation of A549 cell. Meanwhile, the tumor cell-derived exosome miR-10b promoted the invasion of A549 cell and EMT by promoting the M2 polarization of macrophages.
    CONCLUSIONS: Tumor cell-derived exosome miR-10b promotes A549 cell invasion and EMT through M2 macrophage polarization.
    Keywords:  A549; Epithelial mesenchymal transition; Exosome; Invasion; M2 macrophage polarization; miR-10b
    DOI:  https://doi.org/10.3779/j.issn.1009-3419.2022.101.50
  5. Int J Mol Sci. 2022 Dec 27. pii: 464. [Epub ahead of print]24(1):
    Comparative Analysis of Tumor-Associated microRNAs and Tetraspanines from Exosomes of Plasma and Ascitic Fluids of Ovarian Cancer Patients.
    Natalia Yunusova, Ekaterina Dzhugashvili, Alena Yalovaya, Larisa Kolomiets, Aleksei Shefer, Alina Grigor'eva, Alexey Tupikin, Irina Kondakova, Svetlana Tamkovich.
      Ovarian cancer (OC) is one of the most common and fatal types of gynecological cancer. In the early phase of OC detection, the current treatment and diagnostic methods are not efficient and sensitive enough. Therefore, it is crucial to explore the mechanisms of OC metastasis and discover valuable factors for early diagnosis of female cancers and novel therapeutic strategies for metastasis. Exosomes are known to be involved in the development, migration, and invasion of cancer cells, and their cargo could be useful for the non-invasive biopsy development. CD151- and Tspan8-positive exosomes are known to support the degradation of the extracellular matrix, and are involved in stroma remodeling, angiogenesis and cell motility, as well as the association of miR-24 and miR-101 with these processes. The objective of this study was to explore the relationship of these components of exosomal cargo, in patients with OC, to clarify the clinical significance of these markers in liquid biopsies. The levels of tetraspanins Tspan8+ and CD151+ exosomes were significantly higher in plasma exosomes of OC patients compared with healthy females (HFs). The relative levels of miR-24 and miR-101 in plasma exosomes of HFs were significantly higher than in plasma exosomes of OC patients, while the levels of these microRNAs in exosomes from plasma and ascites of ill females showed no difference. Our study revealed a strong direct correlation between the change in the ascites exosomes CD151+Tspan8+ subpopulation level and the expression levels of the ascites (R = 0.81, p < 0.05) and plasma exosomal miR-24 (R = 0.74, p < 0.05) in OC patients, which confirms the assumption that exosomal cargo act synergistically to increase cellular motility, affecting cellular processes and signaling. Bioinformatics analysis confirmed the involvement of CD151 and Tspan8 tetraspanins and genes controlled by miR-24-3p and miR-101 in signaling pathways, which are crucial for carcinogenesis, demonstrating that these tetraspanins and microRNAs are potential biomarkers for OC screening, and predictors of poor clinicopathological behavior in tumors.
    Keywords:  CD151; Tspan8; exosomes; miR-101; miR-24-3p; ovarian cancer; tumor-specific microRNAs
    DOI:  https://doi.org/10.3390/ijms24010464
  6. Mater Today Bio. 2023 Feb;18 100538
    Advanced technologies for molecular diagnosis of cancer: State of pre-clinical tumor-derived exosome liquid biopsies.
    Lin Li, Lili Zhang, Katelynn C Montgomery, Li Jiang, Christopher J Lyon, Tony Y Hu.
      Exosomes are membrane-defined extracellular vesicles (EVs) approximately 40-160 ​nm in diameter that are found in all body fluids including blood, urine, and saliva. They act as important vehicles for intercellular communication between both local and distant cells and can serve as circulating biomarkers for disease diagnosis and prognosis. Exosomes play a key role in tumor metastasis, are abundant in biofluids, and stabilize biomarkers they carry, and thus can improve cancer detection, treatment monitoring, and cancer staging/prognosis. Despite their clinical potential, lack of sensitive/specific biomarkers and sensitive isolation/enrichment and analytical technologies has posed a barrier to clinical translation of exosomes. This review presents a critical overview of technologies now being used to detect tumor-derived exosome (TDE) biomarkers in clinical specimens that have potential for clinical translation.
    Keywords:  Cancer; Enrichment; Exosome; Isolation; Laboratory developed tests; Molecular diagnosis
    DOI:  https://doi.org/10.1016/j.mtbio.2022.100538
  7. Cancers (Basel). 2022 Dec 29. pii: 205. [Epub ahead of print]15(1):
    Serum-Exosome-Derived miRNAs Serve as Promising Biomarkers for HCC Diagnosis.
    Tao Rui, Xiaobing Zhang, Jufeng Guo, Aizhai Xiang, Ning Tang, Jian Liu, Zonglei Mao.
       BACKGROUND: Serum exosomes are emerging as key liquid biopsy biomarkers for the early diagnosis of cancer. However, the proportion and distribution of small RNA (sRNA) species from serum exosomes of hepatocellular carcinoma (HCC) patients remain unclear. Effective and reliable biomarkers for HCC diagnosis should be explored.
    METHODS: In this study, we aimed to use sRNA sequencing to profile the sRNAs of serum exosomes in HCC and non-tumor donors. The serum exosomes of 124 HCC patients and 46 non-tumor donors were enrolled for detecting the values of the potential biomarkers for the diagnosis of HCC.
    RESULTS: We found that miRNAs accounted for the maximal percentage of all types of sRNAs both in the serum exosomes of HCC patients and non-tumor donors. This indicated that the serum-exosome-derived microRNAs (miRNAs) were the most valuable as potential biomarkers in HCC diagnosis. Then, miRNAs were set as research candidates. In our Chinese cohorts, three serum-exosome-derived miRNAs (miR-122-5p, let-7d-5p, and miR-425-5p) could be promising biomarkers for distinguishing HCC patients from non-tumor donors. In addition, they were preferred for the early diagnosis of HCC. We also presented the base distribution of some novel serum-exosome-derived miRNAs and described the potential values as biomarkers.
    CONCLUSIONS: The results suggested that the serum-exosome-derived miRNAs were the most crucial sRNA species and they highlighted the potential of serum-exosome-derived miRNAs as promising biomarkers for HCC diagnosis.
    Keywords:  HCC; biomarker; exosome; miRNA; sRNA-seq
    DOI:  https://doi.org/10.3390/cancers15010205
  8. Int J Nanomedicine. 2023 ;18 95-114
    Exosomal miR-10527-5p Inhibits Migration, Invasion, Lymphangiogenesis and Lymphatic Metastasis by Affecting Wnt/β-Catenin Signaling via Rab10 in Esophageal Squamous Cell Carcinoma.
    Zhaohua Xiao, Xumei Feng, Yongjia Zhou, Peiwei Li, Junwen Luo, Wenhao Zhang, Jie Zhou, Jiangfeng Zhao, Dong Wang, Yongjie Wang, Zhongxian Tian, Xiaogang Zhao.
       Background: Cancer cell-derived exosomal microRNAs (miRNAs) play critical role in orchestrating intercellular communication between tumor cells and tumor microenvironmental factors, including lymphatic endothelial cells (LECs). Nevertheless, the functions and underlying mechanisms of exosomal miRNAs in lymphatic metastasis and lymphangiogenesis in esophageal squamous cell carcinoma (ESCC) remain unclear.
    Methods: Small RNA sequencing, Gene Expression Omnibus (GEO) analysis and qRT‒PCR were performed to identify the candidate exosomal miRNAs involved in ESCC metastasis. Receiver operating characteristic curve analysis was conducted to evaluate the diagnostic potential of exosomal miR-10527-5p in predicting lymph node metastasis (LNM) status. An in vitro coculture system was used to investigate the effects of exosomal miR-10527-5p on ESCC cells and human LECs (HLECs), followed by a popliteal LNM assay in vivo. The relationship between miR-10527-5p and Rab10 was identified by dual-luciferase reporter, fluorescence in situ hybridization and qRT‒PCR assays. Then, a series of rescue assays were performed to further investigate whether Rab10 is involved in exosomal miR-10527-5p mediated ESCC metastasis.
    Results: MiR-10527-5p was found to be notably reduced in both the plasma exosomes and tumor tissues of ESCC patients with LNM, and plasma exosomal miR-10527-5p had a high sensitivity and specificity for discrimination of LNM status. Moreover, exosome-shuttled miR-10527-5p suppressed the migration, invasion and epithelial-to-mesenchymal transition (EMT) of ESCC cells as well as the migration and tube formation of HLECs via Wnt/β-catenin signaling in vitro and in vivo. Further investigation revealed that Rab10 was a direct target of miR-10527-5p, and re-expression of Rab10 neutralized the inhibitory effects of exosomal miR-10527-5p.
    Conclusion: Our study demonstrated that exosomal miR-10527-5p had a strong capability to predict preoperative LNM status and anti-lymphangiogenic effect. Exosomal miR-10527-5p inhibited lymphangiogenesis and lymphatic metastasis of ESCC in a vascular endothelial growth factor-C (VEGF-C)-independent manner, showing potential as a therapeutic target for ESCC patients.
    Keywords:  biomarker; esophageal squamous cell carcinoma; exosomes; lymphangiogenesis; miR-10527-5p
    DOI:  https://doi.org/10.2147/IJN.S391173
  9. Cancers (Basel). 2022 Dec 23. pii: 82. [Epub ahead of print]15(1):
    Tumor-Derived Extracellular Vesicles in Cancer Immunoediting and Their Potential as Oncoimmunotherapeutics.
    Meysam Najaflou, Mehdi Shahgolzari, Ahmad Yari Khosroushahi, Steven Fiering.
      The tumor microenvironment (TME) within and around a tumor is a complex interacting mixture of tumor cells with various stromal cells, including endothelial cells, fibroblasts, and immune cells. In the early steps of tumor formation, the local microenvironment tends to oppose carcinogenesis, while with cancer progression, the microenvironment skews into a protumoral TME and the tumor influences stromal cells to provide tumor-supporting functions. The creation and development of cancer are dependent on escape from immune recognition predominantly by influencing stromal cells, particularly immune cells, to suppress antitumor immunity. This overall process is generally called immunoediting and has been categorized into three phases; elimination, equilibrium, and escape. Interaction of tumor cells with stromal cells in the TME is mediated generally by cell-to-cell contact, cytokines, growth factors, and extracellular vesicles (EVs). The least well studied are EVs (especially exosomes), which are nanoparticle-sized bilayer membrane vesicles released by many cell types that participate in cell/cell communication. EVs carry various proteins, nucleic acids, lipids, and small molecules that influence cells that ingest the EVs. Tumor-derived extracellular vesicles (TEVs) play a significant role in every stage of immunoediting, and their cargoes change from immune-activating in the early stages of immunoediting into immunosuppressing in the escape phase. In addition, their cargos change with different treatments or stress conditions and can be influenced to be more immune stimulatory against cancer. This review focuses on the emerging understanding of how TEVs affect the differentiation and effector functions of stromal cells and their role in immunoediting, from the early stages of immunoediting to immune escape. Consideration of how TEVs can be therapeutically utilized includes different treatments that can modify TEV to support cancer immunotherapy.
    Keywords:  cancer immunity; exosomes; immune escape; immunoediting; immunosurveillance; tumor microenvironment
    DOI:  https://doi.org/10.3390/cancers15010082
  10. Cancers (Basel). 2022 Dec 25. pii: 123. [Epub ahead of print]15(1):
    Tumor Cell-Derived Exosomal circ-PRKCI Promotes Proliferation of Renal Cell Carcinoma via Regulating miR-545-3p/CCND1 Axis.
    Yiguan Qian, Yang Li, Luwei Xu, Ke Chen, Ning Liu, Xiaobing Yang, Qian Lv, Rongfei Li, Changcheng Zhou, Zheng Xu, Ruipeng Jia, Yu-Zheng Ge.
      Renal cell carcinoma (RCC) originates from the epithelial cells of the renal tubules and has a high degree of malignancy and heterogeneity. Recent studies have found that exosomes regulate intercellular communication via transferring various bioactive molecules, such as circular RNAs (circRNAs), which are critical for cancer progression. However, the role of tumor cell-derived exosomal circRNAs in RCC remains unclear. In this study, we reported the high expression of circ-PRKCI in RCC tissues and serum exosomes. We also found that circ-PRKCI could be transferred exosomally from highly malignant RCC cells to relatively less malignant RCC cells. Tumor cell-derived exosomal circ-PRKCI promoted the proliferation, migration, and invasion of RCC cells, while inhibiting their apoptosis. Mechanistically, we found that circ-PRKCI promoted the proliferation of RCC via the miR-545-3p/CCND1 signaling pathway. Our study is the first to report the potential mechanisms of tumor cell-derived exosomal circ-PRKCI in RCC. In conclusion, this study will provide a new understanding about the molecular mechanisms of RCC progression.
    Keywords:  circ-PRKCI; cyclin D1; exosome; microRNA-545-3p; proliferation; renal cell carcinoma
    DOI:  https://doi.org/10.3390/cancers15010123
  11. ACS Biomater Sci Eng. 2023 Jan 09.
    Exosome-Based Smart Drug Delivery Tool for Cancer Theranostics.
    Rishav Kar, Rajib Dhar, Sayantanee Mukherjee, Sagnik Nag, Sukhamoy Gorai, Nobendu Mukerjee, Dattatreya Mukherjee, Rishabh Vatsa, Mamtha Chandrakanth Jadhav, Arabinda Ghosh, Arikketh Devi, Anand Krishnan, Nanasaheb D Thorat.
      Exosomes are the phospholipid-membrane-bound subpopulation of extracellular vesicles derived from the plasma membrane. The main activity of exosomes is cellular communication. In cancer, exosomes play an important rolefrom two distinct perspectives, one related to carcinogenesis and the other as theragnostic and drug delivery tools. The outer phospholipid membrane of Exosome improves drug targeting efficiency. . Some of the vital features of exosomes such as biocompatibility, low toxicity, and low immunogenicity make it a more exciting drug delivery system. Exosome-based drug delivery is a new innovative approach to cancer treatment. Exosome-associated biomarker analysis heralded a new era of cancer diagnostics in a more specific way. This Review focuses on exosome biogenesis, sources, isolation, interrelationship with cancer and exosome-related cancer biomarkers, drug loading methods, exosome-based biomolecule delivery, advances and limitations of exosome-based drug delivery, and exosome-based drug delivery in clinical settings studies. The exosome-based understanding of cancer will change the diagnostic and therapeutic approach in the future.
    Keywords:  Eexosomes; cancer; cancer biomarker; drug delivery; drug loading methods
    DOI:  https://doi.org/10.1021/acsbiomaterials.2c01329
  12. Mol Cancer. 2023 Jan 06. 22(1): 2
    An exosome-based liquid biopsy signature for pre-operative identification of lymph node metastasis in patients with pathological high-risk T1 colorectal cancer.
    Katsuki Miyazaki, Yuma Wada, Keisuke Okuno, Tatsuro Murano, Yuji Morine, Tetsuya Ikemoto, Yu Saito, Hiroaki Ikematsu, Yusuke Kinugasa, Mitsuo Shimada, Ajay Goel.
       BACKGROUND: According to current guidelines, more than 70% of patients with invasive submucosal colorectal cancer (T1 CRC) undergo a radical operation with lymph node dissection, even though only ~ 10% have lymph node metastasis (LNM). Hence, there is imperative to develop biomarkers that can help robustly identify LNM-positive patients to prevent such overtreatments. Given the emerging interest in exosomal cargo as a source for biomarker development in cancer, we examined the potential of exosomal miRNAs as LNM prediction biomarkers in T1 CRC.
    METHODS: We analyzed 200 patients with high-risk T1 CRC from two independent cohorts, including a training (n = 58) and a validation cohort (n = 142). Cell-free and exosomal RNAs from pre-operative serum were extracted, followed by quantitative reverse-transcription polymerase chain reactions for a panel of miRNAs.
    RESULTS: A panel of four miRNAs (miR-181b, miR-193b, miR-195, and miR-411) exhibited robust ability for detecting LNM in the exosomal vs. cell-free component. We subsequently established a cell-free and exosomal combination signature, successfully validated in two independent clinical cohorts (AUC, 0.84; 95% CI 0.70-0.98). Finally, we developed a risk-stratification model by including key pathological features, which reduced the false positive rates for LNM by 76% without missing any true LNM-positive patients.
    CONCLUSIONS: Our novel exosomal miRNA-based liquid biopsy signature robustly identifies T1 CRC patients at risk of LNM in a preoperative setting. This could be clinically transformative in reducing the significant overtreatment burden of this malignancy.
    Keywords:  Cell-free miRNA; Exosomal miRNA; Liquid biopsy; Lymph node metastasis; T1 CRC
    DOI:  https://doi.org/10.1186/s12943-022-01685-8
  13. Front Cell Dev Biol. 2022 ;10 1008901
    MiRNAs from serum-derived extracellular vesicles as biomarkers for uveal melanoma progression.
    Joanna Patrycja Wróblewska, Michał Stefan Lach, Marcin Rucinski, Igor Piotrowski, Lukasz Galus, Wiktoria Maria Suchorska, Stephanie Kreis, Andrzej Marszałek.
      Uveal melanoma (UM) is a rare type of malignancy that originates from melanocytes in the choroid, iris and the eye's ciliary body. Biomarkers for early detection and progression of UM, especially the molecular traits governing the development of metastasis, are still not available in clinical practice. One extensively studied components of liquid biopsies are extracellular vesicles. Due to their unique molecular cargo, they can contribute to early cancer development and at the same time carry markers for disease onset and progression. For characterisation of the miRNA profiles present in circulating serum-derived exosomes of patients with diagnosed primary and metastatic UM, we have analyzed the miRNA cargos using next-generation sequencing followed by RT-qPCR validation in a cohort of patients (control n = 20; primary n = 9; metastatic n = 11). Nine miRNAs differentiating these patient groups have been established. We show that hsa-miR-144-5p and hsa-miR-191-5p are the most promising biomarker candidates, allowing the categorization of patients into local and advanced UM. Additionally, the comparison of miRNA expression levels in exosomes derived from UM patients with those derived from healthy donors revealed that hsa-miR-191-5p, -223-3p, -483-5p, -203a has the potential to be used as an early marker for the presence of UM. This pilot study reveals that miRNAs extracted from circulating exosomes could be exploited as potential biomarkers in UM diagnosis and, more importantly, for indicating metastatic spread.
    Keywords:  biomarkers; extracellular vesicles; liquid biopsy; miRNA; microRNA; uveal melanoma
    DOI:  https://doi.org/10.3389/fcell.2022.1008901
  14. Cancers (Basel). 2022 Dec 23. pii: 80. [Epub ahead of print]15(1):
    Exosome-Derived microRNA: Implications in Melanoma Progression, Diagnosis and Treatment.
    Qiang Ye, Zi Li, Yang Li, Yirong Li, Yan Zhang, Runlin Gui, Yue Cui, Qi Zhang, Lu Qian, Yuyan Xiong, Yi Yu.
      Melanoma is a malignant and aggressive cancer, and its progression is greatly affected by interactions between melanoma cells and their surroundings. Exploration on mechanism of melanoma and improved diagnostic and therapeutic strategies are becoming increasingly important. Unlike extracellular messengers that mainly work on targeted cells through corresponding receptors, exosomes are essential intercellular messengers that deliver biologically active substances such as nucleic acids and proteins to target cells for cell-cell communication. Of them, microRNAs (miRNAs) are common and important exosomal components that can regulate the expression of a wide range of target genes. Accordingly, exosome-derived miRNAs play a significant role in melanoma progression, including invasion and metastasis, microenvironment establishment, angiogenesis, and immune escape. MiRNA signatures of exosomes are specific in melanoma patients compared to healthy controls, thus circulating miRNAs, especially exosomal miRNAs, become potential diagnostic markers and therapeutic targets for melanoma. This review aims to summarize recent studies on the role of exosomal miRNAs in melanoma as well as ongoing efforts in melanoma treatment.
    Keywords:  diagnosis; exosome; melanoma; microRNA; treatment
    DOI:  https://doi.org/10.3390/cancers15010080
  15. Cancers (Basel). 2022 Dec 29. pii: 212. [Epub ahead of print]15(1):
    Combination of Small Extracellular Vesicle-Derived Annexin A2 Protein and mRNA as a Potential Predictive Biomarker for Chemotherapy Responsiveness in Aggressive Triple-Negative Breast Cancer.
    Priyanka P Desai, Kalyani Narra, Johanna D James, Harlan P Jones, Amit K Tripathi, Jamboor K Vishwanatha.
      Small extracellular vesicles (sEVs), mainly exosomes, are nanovesicles that shed from the membrane as intraluminal vesicles of the multivesicular bodies, serve as vehicles that carry cargo influential in modulating the tumor microenvironment for the multi-step process of cancer metastasis. Annexin A2 (AnxA2), a calcium(Ca2+)-dependent phospholipid-binding protein, is among sEV cargoes. sEV-derived AnxA2 (sEV-AnxA2) protein is involved in the process of metastasis in triple-negative breast cancer (TNBC). The objective of the current study is to determine whether sEV-AnxA2 protein and/or mRNA could be a useful biomarkers to predict the responsiveness of chemotherapy in TNBC. Removal of Immunoglobulin G (IgG) from the serum as well as using the System Bioscience's ExoQuick Ultra kit resulted in efficient sEV isolation and detection of sEV-AnxA2 protein and mRNA compared to the ultracentrifugation method. The standardized method was applied to the twenty TNBC patient sera for sEV isolation. High levels of sEV-AnxA2 protein and/or mRNA were associated with stage 3 and above in TNBC. Four patients who responded to neoadjuvant chemotherapy had high expression of AnxA2 protein and/or mRNA in sEVs, while other four who did not respond to chemotherapy had low levels of AnxA2 protein and mRNA in sEVs. Our data suggest that the sEV-AnxA2 protein and mRNA could be a combined predictive biomarker for responsiveness to chemotherapy in aggressive TNBC.
    Keywords:  annexin A2; biomarker; neo-adjuvant chemotherapy; small extracellular vesicles; triple-negative breast cancer
    DOI:  https://doi.org/10.3390/cancers15010212
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