bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2022–09–18
seventeen papers selected by
Muhammad Rizwan, COMSATS University
  1. Exosomes and cancer - Diagnostic and prognostic biomarkers and therapeutic vehicle.
  2. Impaired Autophagy Response in Hepatocellular Carcinomas Enriches Glypican-3 in Exosomes, Not in the Microvesicles.
  3. Bile-derived exosome noncoding RNAs as potential diagnostic and prognostic biomarkers for cholangiocarcinoma.
  4. Functions and clinical applications of exosomes in pancreatic cancer.
  5. Construction of a novel exosomes-related gene signature in hepatocellular carcinoma.
  6. The history of small extracellular vesicles and their implication in cancer drug resistance.
  7. Small extracellular vesicles: from promoting pre-metastatic niche formation to therapeutic strategies in breast cancer.
  8. Extracellular vesicle secretion by leukemia cells in vivo promotes CLL progression by hampering antitumor T-cell responses.
  9. Extracellular vesicle contents as non-invasive biomarkers in ovarian malignancies.
  10. Exosomal lncRNA PCAT1 Promotes Tumor Circulating Cell-Mediated Colorectal Cancer Liver Metastasis by Regulating the Activity of the miR-329-3p/Netrin-1-CD146 Complex.
  11. AS1411 aptamer-functionalized exosomes in the targeted delivery of doxorubicin in fighting colorectal cancer.
  12. Engineered Exosomes Loaded with miR-563 Inhibit Lung Cancer Growth.
  13. Exosome secretion and cellular response of DU145 and PC3 after exposure to alpha radiation.
  14. In Vivo Imaging for the Visualization of Extracellular Vesicle-Based Tumor Therapy.
  15. Mesenchymal stem cell-derived exosomes in cancer therapy resistance: recent advances and therapeutic potential.
  16. Exosome Derived from Mesenchymal Stem Cells Alleviates Pathological Scars by Inhibiting the Proliferation, Migration and Protein Expression of Fibroblasts via Delivering miR-138-5p to Target SIRT1.
  17. Mesenchymal stem cells- derived exosomes inhibit the expression of Aquaporin-5 and EGFR in HCT-116 human colorectal carcinoma cell line.
  1. Oncogenesis. 2022 Sep 15. 11(1): 54
    Exosomes and cancer - Diagnostic and prognostic biomarkers and therapeutic vehicle.
    Xia Wang, Lu Tian, Jingyi Lu, Irene Oi-Lin Ng.
      Exosomes belong to a subpopulation of extracellular vesicles secreted by the dynamic multistep endocytosis process and carry diverse functional molecular cargoes, including proteins, lipids, nucleic acids (DNA, messenger and noncoding RNA), and metabolites to promote intercellular communication. Proteins and noncoding RNA are among the most abundant contents in exosomes; they have biological functions and are selectively packaged into exosomes. Exosomes derived from tumor, stromal and immune cells contribute to the multiple stages of cancer progression as well as resistance to therapy. In this review, we will discuss the biogenesis of exosomes and their roles in cancer development. Since specific contents within exosomes originate from their cells of origin, this property allows exosomes to function as valuable biomarkers. We will also discuss the potential use of exosomes as diagnostic and prognostic biomarkers or predictors for different therapeutic strategies for multiple cancers. Furthermore, the applications of exosomes as direct therapeutic targets or engineered vehicles for drugs are an important field of exosome study. Better understanding of exosome biology may pave the way to promising exosome-based clinical applications.
    DOI:  https://doi.org/10.1038/s41389-022-00431-5
  2. J Hepatocell Carcinoma. 2022 ;9 959-972
    Impaired Autophagy Response in Hepatocellular Carcinomas Enriches Glypican-3 in Exosomes, Not in the Microvesicles.
    Ali Riza Koksal, Paul Thevenot, Yucel Aydin, Kelley Nunez, Tyler Sandow, Kyle Widmer, Leela Nayak, John Scott, Molly Delk, Martin W Moehlen, Ari J Cohen, Srikanta Dash.
       Background and Aim: HCC development in liver cirrhosis is associated with impaired autophagy leading to increased production of extracellular vesicles (EVs) including exosomes and microvesicles. The goal of the study is to determine which of these particles is primarily involved in releasing of HCC-specific biomarker glypican-3 (GPC3) when autophagy is impaired.
    Methods: Streptavidin-coated magnetic beads were coupled with either biotinylated CD63 or Annexin A1 antibodies. Coupled beads were incubated with EVs isolated from either HCC culture or serum. EVs captured by immuno-magnetic beads were then stained with FITC or PE fluorescent-conjugated antibodies targeting exosomes (CD81), and microvesicles (ARF6). The percentage of GPC3 enrichment in the microvesicles and exosomes was quantified by flow cytometry. The impact of autophagy modulation on GPC3 enrichment in exosomes and microvesicles was assessed by treating cells with Torin 1 and Bafilomycin A1. For clinical validation, GPC3 content was quantified in microvesicles, and exosomes were isolated from the serum of patients with a recent HCC diagnosis.
    Results: The immune-magnetic bead assay distinguishes membrane-derived microvesicles from endosome-derived exosomes. The GPC3 expression was only seen in the CD63 beads group but not in the Annexin A1 beads group, confirming that in HCC, GPC3 is preferentially released through exosomes. Furthermore, we found that autophagy induction by Torin1 decreased GPC3-positive exosome secretion and decreased microvesicle release. Conversely, autophagy inhibition by Bafilomycin A1 increased the secretion of GPC3-positive exosomes. Serum analysis showed CD81+ve EVs were detected in exosomes and ARF6+ve vesicles were detected in microvesicles, suggesting that immunoaffinity assay is specific. The exosomal GPC3 enrichment was confirmed in isolated EVs from the serum of patients with HCC. The frequency of GPC3-positive exosomes was higher in patients with HCC (12.4%) compared to exosomes isolated from non-cirrhotic and healthy controls (3.7% and 1.3% respectively, p<0.001).
    Conclusion: Our results show that GPC3 is enriched in the endolysosomal compartment and released in exosome fractions when autophagy is impaired.
    Keywords:  biomarker; exosome; glypican 3; hepatocellular carcinoma; magnetic beads
    DOI:  https://doi.org/10.2147/JHC.S376210
  3. Front Oncol. 2022 ;12 985089
    Bile-derived exosome noncoding RNAs as potential diagnostic and prognostic biomarkers for cholangiocarcinoma.
    Yan Pan, Shijie Shao, Hang Sun, Huafeng Zhu, Haixing Fang.
       Background: Cholangiocarcinoma (CCA) is one of the most aggressive malignancies, lacking novel diagnostic and prognostic biomarkers. Exosome noncoding RNAs (ncRNA) were previously proposed as a potential source of biomarkers in several cancers. This study aimed to interpret the value of specific bile-derived ncRNA as predictors for early diagnosis and prognosis of CCA.
    Methods: We recruited 100 patients who received endoscopic retrograde cholangiopancreatography at our hospital for bile duct obstruction due to CCA (n = 50) and biliary stone (n = 50). They were further divided into training set and validation set (3:2). A panel of CCA-specific ncRNAs including 5 miRNAs (PMID: 30165035) and 2 lncRNAs (PMID: 29050258) were detected in both serum and bile exosomes. The diagnostic accuracy was assessed using the area under the receiver operating characteristic curve. Logistic analysis was used to classify the potential predictors of CCA and further establish the diagnostic model. And the prognostic value of the ncRNAs was also assessed.
    Results: Exosomes were successfully collected from bile and serum. Exosomal miR-141-3p, miR-200a-3p, miR-200c-3p in serum and bile, as well as miR-200b-3p and ENST00000588480.1 in bile showed AUCs of >0.70 in the diagnosis of CCA. Bile exosomal miR-200c-3p displayed the best diagnostic value with the AUC of 0.87. The combination of serum CA19-9 into the model could increase the AUC to 0.906. Bile exosomal miR-200a-3p and miR-200c-3p were found to be independent predictors of CCA. Among exosomal ncRNAs in human bile and blood, 3 (serum and bile exosomal miR-200c-3p, bile exosomal miR-200a-3p) showed significant value in predicting cancer recurrence and 1 (serum exosomal miR-200c-3p) had great predictive ability of cancer death. High levels of serum exosomal miR-200c-3p showed unfavorable tumor-free survival and overall survival.
    Conclusion: The bile exosomal miR-200 family, particularly miR-200c-3p, was verified to be a potential biomarker for the early detection of CCA. The diagnostic ability of exosomal ncRNAs in human bile is better than that in blood. Moreover, high levels of bile exosomal miR-200a-3p, miR-200c-3p, and serum exosomal miR-200c-3p represented adverse clinical outcomes.
    Keywords:  bile; biomarker; cholangiocarcinoma; exosome; lncRNA; microRNA
    DOI:  https://doi.org/10.3389/fonc.2022.985089
  4. Mol Biol Rep. 2022 Sep 12.
    Functions and clinical applications of exosomes in pancreatic cancer.
    Zhichen Jiang, Huiju Wang, Yiping Mou, Li Li, Weiwei Jin.
      Pancreatic cancer (PC) is one of the most malignant tumors and has an abysmal prognosis, with a 5-year survival rate of only 11%. At present, the main clinical dilemmas in PC are the lack of biomarkers and the unsatisfactory therapeutic effects. The treatments for and outcomes of PC have improved, but remain unsatisfactory. Exosomes are nanosized extracellular vesicles, and an increasing number of studies have found that exosomes play an essential role in tumor pathology. In this review, we describe the process of exosome biogenesis, as well as exosome extraction methods and identification strategies, and we then explain in detail the roles and mechanisms of exosomes in invasion, metastasis, chemoresistance and immunosuppression in PC. Finally, we summarize the clinical applications of exosomes. Our observations indicate that exosomes represent a novel direction in the clinical treatment of PC.
    Keywords:  Biomarker; Exosome; Extracellular vesicles; Pancreatic cancer; Therapy
    DOI:  https://doi.org/10.1007/s11033-022-07765-8
  5. Front Cell Dev Biol. 2022 ;10 997734
    Construction of a novel exosomes-related gene signature in hepatocellular carcinoma.
    Qiqi Tao, Kai Zhu, Yating Zhan, Rongrong Zhang, Zhichao Lang, Zhengping Yu, Meng Wang.
      Background: Exosomes are extracellular vesicles between 40 and 150 nm in diameter and are cargoes for a wide range of small biological molecules. Recent studies have reported that lncRNAs, miRNAs, circRNAs in serum exosomes may serve as biomarkers to predict hepatocellular carcinoma (HCC) prognosis. However, the prognostic values of exosomes-related mRNAs in HCC are still unclear. Methods: Data of HCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The serum exosome sequencing data of HCC patients and healthy individuals were obtained from the exobase database. Univariate cox regression analysis was used to identify prognostic exosomes-related genes. LASSO and multivariate cox regression analyses were applied to construct prognostic signature. Results: 22 exosomes-related mRNAs differentially expressed between HCC tissues and normal tissues were identified. Then, 8 prognostic exosomes-related mRNAs were screened. Subsequently, G6PD and ADAMTS5, selected by LASSO and multivariate cox regression analyses, were used to construct a prognostic signature. The patients with high-risk scores had a poor prognosis in TCGA cohort as well as ICGC cohort. Notably, this prognostic signature was also validated in a local cohort collected from the First Affiliated Hospital of Wenzhou Medical University. Receiver Operating Characteristic (ROC) analyses indicated that the signature had a good performance in all the cohorts. The gene set enrichment analysis revealed that this signature was associated with cell cycle and metabolism pathways. Immune infiltration analysis indicated that the patients with high-risk scores had a higher M0 macrophages infiltration. The univariate and multivariate cox regression analyses identified that the risk score is an independent risk factor for HCC. In addition, a nomogram containing age, gender, stage and risk score was constructed to precisely predict HCC prognosis. Conclusion: In conclusion, we develop a novel exosomes-related gene signature that helps to predict HCC prognosis.
    Keywords:  exosome; hepatocellular carcinoma; immune infiltration; nomogram; prognostic signature
    DOI:  https://doi.org/10.3389/fcell.2022.997734
  6. Front Oncol. 2022 ;12 948843
    The history of small extracellular vesicles and their implication in cancer drug resistance.
    Stefano Palazzolo, Vincenzo Canzonieri, Flavio Rizzolio.
      Small extracellular vesicles (EVs) in the last 20 years are demonstrated to possess promising properties as potential new drug delivery systems, biomarkers, and therapeutic targets. Moreover, EVs are described to be involved in the most important steps of tumor development and progression including drug resistance. The acquired or intrinsic capacity of cancer cells to resist chemotherapies is one of the greatest obstacles to overcome to improve the prognosis of many patients. EVs are involved in this mechanism by exporting the drugs outside the cells and transferring the drug efflux pumps and miRNAs in recipient cells, in turn inducing drug resistance. In this mini-review, the main mechanisms by which EVs are involved in drug resistance are described, giving a rapid and clear overview of the field to the readers.
    Keywords:  cancer; drug resistance; extra cellular vesicles; oncology; therapy
    DOI:  https://doi.org/10.3389/fonc.2022.948843
  7. Cell Commun Signal. 2022 Sep 12. 20(1): 141
    Small extracellular vesicles: from promoting pre-metastatic niche formation to therapeutic strategies in breast cancer.
    Xiaoxiao Chen, Jiamei Feng, Weili Chen, Shijun Shao, Li Chen, Hua Wan.
      Breast cancer is the most common cancer in females, and to date, the mortality rate of breast cancer metastasis cannot be ignored. The metastasis of breast cancer is a complex, staged process, and the pattern of metastatic spread is not random. The pre-metastatic niche, as an organ-specific home for metastasis, is a favourable environment for tumour cell colonization. As detection techniques improve, the role of the pre-metastatic niche in breast cancer metastasis is being uncovered. sEVs (small extracellular vesicles) can deliver cargo, which is vital for the formation of pre-metastatic niches. sEVs participate in multiple aspects of creating a distant microenvironment to promote tumour invasion, including the secretion of inflammatory molecules, immunosuppression, angiogenesis and enhancement of vascular permeability, as well as regulation of the stromal environment. Here, we discuss the multifaceted mechanisms through which breast cancer-derived sEVs contribute to pre-metastatic niches. In addition, sEVs as biomarkers and antimetastatic therapies are also discussed, particularly their use in transporting exosomal microRNAs. The study of sEVs may provide insight into immunotherapy and targeted therapies for breast cancer, and we also provide an overview of their potential role in antitumour metastasis. Video Abstract.
    Keywords:  Breast cancer; Immunotherapy; Metastasis; MiRNA; Pre-metastatic niche; sEVs
    DOI:  https://doi.org/10.1186/s12964-022-00945-w
  8. Blood Cancer Discov. 2022 Sep 15. pii: BCD-22-0029. [Epub ahead of print]
    Extracellular vesicle secretion by leukemia cells in vivo promotes CLL progression by hampering antitumor T-cell responses.
    Ernesto Gargiulo, Elodie Viry, Pablo Elias Morande, Anne Largeot, Susanne Gonder, Feng Xian, Nikolaos Ioannou, Mohaned Benzarti, Felix Bruno Kleine Borgmann, Michel Mittelbronn, Gunnar Dittmar, Petr V Nazarov, Johannes Meiser, Basile Stamatopoulos, Alan G Ramsay, Etienne Moussay, Jerome Paggetti.
      Small extracellular vesicles (sEV, or exosomes) communication among cells in the tumor microenvironment has been modeled mainly in cell culture, while their relevance in cancer pathogenesis and progression in vivo is less characterized. Here we investigated cancer-microenvironment interactions in vivo using mouse models of chronic lymphocytic leukemia (CLL). sEV isolated directly from CLL tissue were enriched in specific miRNA and immune checkpoint ligands. Distinct molecular components of tumor-derived sEV altered CD8+ T-cell transcriptome, proteome and metabolome leading to decreased functions and cell exhaustion ex vivo and in vivo. Using antagomiRs and blocking antibodies, we defined specific cargo-mediated alterations on CD8+ T-cells. Abrogating sEV biogenesis by Rab27a/b knockout dramatically delayed CLL pathogenesis. This phenotype was rescued by exogenous leukemic sEV or CD8+ T-cell depletion. Finally, high expression of sEV-related genes correlated with poor outcomes in CLL patients, suggesting sEV profiling as prognostic tool. In conclusion, sEV shape the immune microenvironment during CLL progression.
    DOI:  https://doi.org/10.1158/2643-3230.BCD-22-0029
  9. Mol Ther Oncolytics. 2022 Sep 15. 26 347-359
    Extracellular vesicle contents as non-invasive biomarkers in ovarian malignancies.
    Lindsey A McAlarnen, Prachi Gupta, Reena Singh, Sunila Pradeep, Pradeep Chaluvally-Raghavan.
      Ovarian cancer most commonly presents at an advanced stage where survival is approximately 30% compared with >80% if diagnosed and treated before disease spreads. Diagnostic capabilities have progressed from surgical staging via laparotomy to image-guided biopsies and immunohistochemistry staining, along with advances in technology and medicine. Despite improvements in diagnostic capabilities, population-level screening for ovarian cancer is not recommended. Extracellular vesicles (EVs) are 40-150 nm structures formed when the cellular lipid bilayer invaginates. These structures function in cell signaling, immune responses, cancer progression, and establishing the tumor microenvironment. EVs are found in nearly every bodily fluid, including serum, plasma, ascites, urine, and effusion fluid, and contain molecular cargo from their cell of origin. This cargo can be analyzed to yield information about a possible malignancy. In this review we describe how the cargo of EVs has been studied as biomarkers in ovarian cancer. We bring together studies analyzing evidence for various cargos as ovarian cancer biomarkers. Then, we describe the role of EVs in modulation of the tumor microenvironment. This review also summarizes the therapeutic and translational potential of EVs for their optimal utilization as non-invasive biomarkers for novel treatments against cancer.
    Keywords:  biomarkers; epithelial cancer; extracellular vesicles; liquid biopsy; ovarian cancer; solid tumor; tumor microenvironment
    DOI:  https://doi.org/10.1016/j.omto.2022.08.005
  10. J Immunol Res. 2022 ;2022 9916228
    Exosomal lncRNA PCAT1 Promotes Tumor Circulating Cell-Mediated Colorectal Cancer Liver Metastasis by Regulating the Activity of the miR-329-3p/Netrin-1-CD146 Complex.
    Xingbao Fang, Yongping Xu, Kezhi Li, Peiwan Liu, Hong Zhang, Yang Jiang, Jianwei Tang, Yuehong Li.
       Objective: This study explored the colorectal cancer exosome lncRNA prostate cancer associated transcript 1- (PCAT1) mediated circulating tumors and the mechanism of cell colorectal cancer liver metastasis.
    Methods: Exosomes were extracted from the primary colorectal cancer (CRC) cell lines HCT116 and SW480 and cultured with T84 and human umbilical vein endothelial (HUVE) cells. The expression of PCAT1 and miR-329-3p was detected by real-time quantitative polymerase chain reaction (RT-qPCR), the expression of Netrin-1, CD146, and epithelial mesenchymal transition (EMT) related proteins was detected by Western blot, the proliferation activity of T84 cells was detected by cell counting kit 8 (CCK-8), and cell migration was detected by Transwell. The expression of the F-actin signal was detected by immunofluorescence after coculture of exosomes with human umbilical vein endothelial cells (HUVECs). Changes in subcutaneous tumor and liver nodule size after PCAT1 deletion were observed in a mouse model of liver metastasis from rectal cancer.
    Results: PCAT1 expression was upregulated in primary cell lines and their exosomes. After exosomes were cocultured with colorectal cancer tumor circulating T84 cells, the expression of Netrin-1 and CD146 was upregulated, the expression of miR-329-3p was downregulated, the proliferation and migration ability of T84 cells were enhanced, and EMT occurred. After knocking down PCAT1, the above phenomenon was reversed. Similarly, after exosomes were cocultured with HUVECs, the expression of the F-actin signal increased, and after PCAT1 was knocked down, the F-actin signal also decreased. PCAT1 regulates miR-329-3p/Netrin-1 and affects the biological behavior of T84 and F-actin signal expression in HUVECs. In a mouse model of colorectal cancer liver metastasis, knocking down PCAT1 significantly reduced the nodules formed by liver metastasis in mice.
    Conclusions: LncRNA PCAT1 derived from colorectal cancer exosomes regulates the activity of the Netrin-1-CD146 complex in circulating tumor cells (CTCs) to promote the occurrence of colorectal cancer EMT and liver metastasis and provides new molecular targets for the treatment of colorectal cancer liver metastasis.
    DOI:  https://doi.org/10.1155/2022/9916228
  11. Biomed Pharmacother. 2022 Sep 12. pii: S0753-3322(22)01079-4. [Epub ahead of print]155 113690
    AS1411 aptamer-functionalized exosomes in the targeted delivery of doxorubicin in fighting colorectal cancer.
    Nashmin Fayazi Hosseini, Razieh Amini, Mohammad Ramezani, Massoud Saidijam, Seyed Mahmoud Hashemi, Rezvan Najafi.
      Severe side effects of chemotherapy agents on vital organs are the major causes of cancer-related mortality, not merely cancer disease. Encapsulating chemotherapeutic molecules in nanocarriers is a justifiable solution in decreasing the risk of their side effects and boosting the efficiency of treatment. The present study has developed the doxorubicin (DOX)-loaded AS1411 (anti-nucleolin) aptamer surface-functionalized exosome (DOX-Apt-Exo) to treat colorectal cancer in both in-vitro and in-vivo experimental models. HEK293-derived exosomes were loaded with DOX through the incubation method with a nearly 13% encapsulation efficiency. Afterwards, the 5-terminal carboxyl group of AS1411-aptamer was converted into amine-reactive NHS esters with EDC/NHS amide coupling chemistry before being conjugated to the amine groups on the exosome surface. DLS and TEM estimated the designed formulation (DOX-Apt-Exo) size of about 200 nm. Aptamer-binding affinity and cellular uptake of DOX-Apt-Exo by nucleolin-overexpressing cancer cells were depicted through fluorescence microscopy. Comparing the in-vitro cytotoxicity impact of DOX-loaded exosomes, either targeted or non-targeted by MTT assay, clearly verified a high effectiveness of ligand-receptor mediated target therapy. Subsequently, in-vivo experiments which were conducted on four groups of ectopic mouse models of colon cancer (5 in each group) demonstrated the tumor growth suppression through professional long-term accumulation and retention of DOX-Apt-Exo at the tumor site by ligand-receptor interaction. The results suggested that AS1411 aptamer-functionalized exosomes can be recommended as a safe and effective system to site-specific drug delivery in possible clinical applications of colon cancer.
    Keywords:  AS1411; Colorectal cancer; Doxorubicin; Exosome; Nucleolin
    DOI:  https://doi.org/10.1016/j.biopha.2022.113690
  12. J Oncol. 2022 ;2022 6141857
    Engineered Exosomes Loaded with miR-563 Inhibit Lung Cancer Growth.
    Weiwei Gao, Nan Yang, Chunyang Yin, Yi Zeng, Xiaoping Zhu.
      The malignancy of lung cancer (LC) is serious in the world. Exosomes are well-known natural nanovesicles, which are reported to have the potential to carry functional miRNAs as natural carriers and deliver chemotherapeutic drugs. However, the safety and functions of the engineered exosomes for delivering miRNA for the treatment of LC remain to be evaluated. In this study, we found that miR-563 is related to lung cancer from GeneCard database. RT-qPCR and in situ hybridization (ISH) were used to assess miR-563 expression in clinical samples. We prepared and verified the engineered exosomes loaded with miR-563 both in vitro and in vivo. In vitro, flow cytometry, Western blot, and other experimental methods were performed to evaluate the antitumor effect of miR-563 loaded exosomes. In in vivo, the LC mouse model was used to observe the effect of the prepared exosomes. The safety of using this exosomes was accessed by liver function test, hematological analysis, and H&E staining in major organs of the mice. Our findings indicated that the miR-563 loaded engineered exosomes inhibit the A549 cells growth in vitro, by inhibiting the tumor cell proliferation, migration, and invasion and promoting apoptosis. In in vivo, these engineered exosomes were enriched in tumor tissue after injecting to LC model mice and impacted tumor tissue by inhibiting the tumor volume and tumor weight. Importantly, our study indicated that miR-563 loaded engineered exosomes have the potential for clinical application for LC treatment with acceptable safety profiles. Our findings indicate a novel potential therapeutic target for lung cancer patients by miR-563 loaded engineered exosomes.
    DOI:  https://doi.org/10.1155/2022/6141857
  13. Radiat Environ Biophys. 2022 Sep 13.
    Exosome secretion and cellular response of DU145 and PC3 after exposure to alpha radiation.
    Beata Pszczółkowska, Wioletta Olejarz, Mateusz Filipek, Adrianna Tartas, Grażyna Kubiak-Tomaszewska, Aleksandra Żołnierzak, Katarzyna Życieńska, Józef Ginter, Tomasz Lorenc, Beata Brzozowska.
      Exosomes are spherical membrane nanovesicles secreted from cells, and they play an important role in tumor immune response, metastasis, angiogenesis, and survival. Studies investigating exosomes isolated from cells exposed to photon radiation commonly used in conventional radiotherapy demonstrate the influence of this type of radiation on exosome characteristics and secretion. There is currently no research investigating the effects of densely ionizing particles such as protons and alpha radiation on exosomes. Thus we have evaluated the cellular response of human prostate cancer cells exposed to 0, 2, and 6 Gy of alpha radiation emitted from the Am-241 source. Irradiated PC3 and DU145 cell lines, characterized by differences in radiosensitivity, were studied using apoptosis, LDH, and IL-6 assays. Additionally, the corresponding concentration and size of isolated exosomes were measured using NTA. We found that exposure to ionizing radiation resulted in gross changes in viability and cell damage. There were increased amounts of apoptotic or necrotic cells as a function of radiation dose. We demonstrated that irradiated PC3 cells secrete higher quantities of exosomes compared to DU145 cells. Additionally, we also found no statistical difference in exosome size for control and irradiated cells.
    Keywords:  Alpha particles; Exosomes; High LET radiation; Prostate cancer
    DOI:  https://doi.org/10.1007/s00411-022-00991-5
  14. ChemistryOpen. 2022 Sep;11(9): e202200124
    In Vivo Imaging for the Visualization of Extracellular Vesicle-Based Tumor Therapy.
    Anqi Jiang, Weidong Nie, Hai-Yan Xie.
      Extracellular vesicles (EVs) exhibiting versatile biological functions provide promising prospects as natural therapeutic agents and drug delivery vehicles. For future clinical translation, revealing the fate of EVs in vivo, especially their accumulation at lesion sites, is very important. The continuous development of in vivo imaging technology has made it possible to track the real-time distribution of EVs. This article reviews the applications of mammal-, plant-, and bacteria-derived EVs in tumor therapy, the labeling methods of EVs for in vivo imaging, the advantages and disadvantages of different imaging techniques, and possible improvements for future work.
    DOI:  https://doi.org/10.1002/open.202200124
  15. Mol Cancer. 2022 Sep 13. 21(1): 179
    Mesenchymal stem cell-derived exosomes in cancer therapy resistance: recent advances and therapeutic potential.
    Zhengjun Lin, Yanlin Wu, Yiting Xu, Guoqing Li, Zhihong Li, Tang Liu.
      Mesenchymal stem cells (MSCs) are multipotent stromal cells that can be obtained from various human tissues and organs. They can differentiate into a wide range of cell types, including osteoblasts, adipocytes and chondrocytes, thus exhibiting great potential in regenerative medicine. Numerous studies have indicated that MSCs play critical roles in cancer biology. The crosstalk between tumour cells and MSCs has been found to regulate many tumour behaviours, such as proliferation, metastasis and epithelial-mesenchymal transition (EMT). Multiple lines of evidence have demonstrated that MSCs can secrete exosomes that can modulate the tumour microenvironment and play important roles in tumour development. Notably, very recent works have shown that mesenchymal stem cell-derived exosomes (MSC-derived exosomes) are critically involved in cancer resistance to chemotherapy agents, targeted-therapy drugs, radiotherapy and immunotherapy. In this review, we systematically summarized the emerging roles and detailed molecular mechanisms of MSC-derived exosomes in mediating cancer therapy resistance, thus providing novel insights into the clinical applications of MSC-derived exosomes in cancer management.
    Keywords:  Cancer; Exosome; Mesenchymal stem cell; Therapy resistance
    DOI:  https://doi.org/10.1186/s12943-022-01650-5
  16. Int J Nanomedicine. 2022 ;17 4023-4038
    Exosome Derived from Mesenchymal Stem Cells Alleviates Pathological Scars by Inhibiting the Proliferation, Migration and Protein Expression of Fibroblasts via Delivering miR-138-5p to Target SIRT1.
    Wen Zhao, Rui Zhang, Chengyu Zang, Linfeng Zhang, Ran Zhao, Qiuchen Li, Zhanjie Yang, Zhang Feng, Wei Zhang, Rongtao Cui.
       Introduction: The therapies of using exosomes derived from mesenchymal stem cells (MSC-Exo) for wound healing and scar attenuation and micro RNAs (miRNAs) for regulation of genes by translational inhibition and mRNA destabilization obtained great achievements. Silent information regulator 1 (SIRT1) is the silent information, which has an intricate role in many biological processes. However, the effects of SIRT1 and miR-138-5p loaded in MSC-Exo on pathological scars remain unclear.
    Methods: MSC-Exo was isolated and identified by ultracentrifugation, transmission electron microscopy, nanoparticle size measuring instrument and Western blot assays. The relationship between SIRT1 and miR-138-5p was verified by a double-luciferase reporter assay. Cell Counting Kit-8, Τranswell, scratch, and Western blot assays were used to evaluate the proliferation and migration of human skin fibroblasts (HSFs), and the protein expression of SIRT1, NF-κB, α-SMA and TGF-β1 in HSFs, respectively. Flow cytometry was used to assess the apoptosis and cell cycle of HSFs affected by SIRT1.
    Results: Our study demonstrated that miR-138-5p loaded in MSC-Exo could attenuate proliferation, migration and protein expression of HSFs-derived NF-κB, α-SMA, and TGF-β1 by targeting to SIRT1 gene, which confirmed the potential effects of MSC-Exo in alleviating pathological scars by performing as a miRNA's delivery vehicle.
    Conclusion: Exosomes derived from MSCs acting as a delivery vehicle to deliver miR-138-5p can downregulate SIRT1 to inhibit the growth and protein expression of HSFs and attenuate pathological scars.
    Keywords:  SIRT1; human skin fibroblasts; mesenchymal stem cell-derived exosomes; miR-138-5p; pathological scars
    DOI:  https://doi.org/10.2147/IJN.S377317
  17. BMC Mol Cell Biol. 2022 Sep 16. 23(1): 40
    Mesenchymal stem cells- derived exosomes inhibit the expression of Aquaporin-5 and EGFR in HCT-116 human colorectal carcinoma cell line.
    Amir Hossein Mansourabadi, Azin Aghamajidi, Fatemeh Faraji, Shirin Taghizadeh, Leila Mohamed Khosroshahi, Mona Bahramkiya, Maryam Azimi.
       BACKGROUND: Aquaporins are channel proteins, form pores in the membrane of biological cells to facilitate the transcellular and transepithelial water movement. The role of Aquaporins in carcinogenesis has become an area of interest. In this study, we aimed to investigate the effects of adipose-derived mesenchymal stem cells secreted exosomes on the expression of aquaporin 5 and EGFR genes in the HCT-116 tumor cell line.
    METHODS AND RESULTS: Surface antigenic profile of Ad-MSCs was evaluated using specific markers. Exosomes were purified from the Ad-MSc supernatant while the quality and the shape of isolated exosomes were assessed by western blot and transmission electron microscopy (TEM) respectively. HCT-116 cells were co-cultured with MSC-conditioned medium (MSC-CM) and/or with 100 μg/ml of MSC-derived exosomes for 48 h and. Real-time PCR was carried out to determine the expression of aquaporin5 and EGFR in HCT-116. Relative expression levels were calculated using the 2-ΔΔct method. Our result showed that AQP5 and EGFR mRNA levels were significantly reduced in CM and/or exosomes treated HCT116 compare to the control group (P-value < 0.05).
    CONCLUSION: The current study showed that MSC derived exosomes could inhibit expression of two important molecules involved in tumor progression. Hence it seems MSCs-derived exosomes may hold a hopeful future as drug delivery vehicles which need the furtherer investigation.
    Keywords:  Aquaporin 5; Exosome; HCT116; Mesenchymal stem cell
    DOI:  https://doi.org/10.1186/s12860-022-00439-0
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