bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2022–12–04
fourteen papers selected by
Muhammad Rizwan, COMSATS University
  1. Exosomal MicroRNAs: Comprehensive Methods from Exosome Isolation to miRNA Extraction and Purity Analysis.
  2. Bladder cancer tissue-derived exosomes suppress ferroptosis of T24 bladder cancer cells by transporting miR-217.
  3. Exosomal MicroRNA Profiling.
  4. Using Natural Killer Cell-derived Exosomes as a Cell-Free Therapy for Leukemia.
  5. Exosomes: special nano-therapeutic carrier for cancers, overview on anticancer drugs.
  6. The application of exosomes in the treatment of triple-negative breast cancer.
  7. Exosomal miR-93-5p from cancer-associated fibroblasts confers malignant phenotypes on bladder cancer cells by targeting PAFAH1B1.
  8. Advances in the Biological Functions of Extracellular Vesicles and their Potential Use in Treating Oral Cancer.
  9. Tumor Cell-Derived Extracellular Vesicles Promote the Growth, Metastasis and Chemoresistance in Cholangiocarcinoma by Delivering microRNA-210 to Downregulate RECK.
  10. Exosomal circNFIX promotes angiogenesis in ovarian cancer via miR-518a-3p/TRIM44 axis.
  11. Dissecting exosome inhibitors: therapeutic insights into small-molecule chemicals against cancer.
  12. Colon cancer exosome-derived biomimetic nanoplatform for curcumin-mediated sonodynamic therapy and calcium overload.
  13. Exosomal circular RNA: a signature for lung cancer progression.
  14. Gastric cancer stem cell-derived exosomes promoted tobacco smoke-triggered development of gastric cancer by inducing the expression of circ670.
  1. Methods Mol Biol. 2023 ;2595 75-92
    Exosomal MicroRNAs: Comprehensive Methods from Exosome Isolation to miRNA Extraction and Purity Analysis.
    D'Agostino Erika, Muro Annamaria, Sgueglia Giulia, Massaro Crescenzo, Dell'Aversana Carmela, Altucci Lucia.
      Exosomes are extracellular vesicles secreted by cells with a key role in a wide range of biological processes including cancer. These vesicles are involved in intercellular communication and deliver diverse cargo molecules, including miRNAs (exo-miRNAs), to recipient cells affecting their physiology. Exo-miRNAs have a role in promoting tumor, progression, metastatization, and remodeling of tumor microenvironment, therefore making them interesting biomarkers to study.Here we provide a detailed technical protocol for exosome isolation (which can be applied to cell culture as well as physiological fluids), validation of their vesicular identity, miRNA extraction, and quantitative and qualitative analysis to evaluate the sample purity and concentration.
    Keywords:  Differential ultracentrifugation; Exo-miRNAs; Exosome RNA extraction; Exosome RNA quality control; Exosome characterization; Exosomes
    DOI:  https://doi.org/10.1007/978-1-0716-2823-2_5
  2. Environ Mol Mutagen. 2022 Dec 02.
    Bladder cancer tissue-derived exosomes suppress ferroptosis of T24 bladder cancer cells by transporting miR-217.
    Zhong-Ming Huang, Hai Wang, Zhi-Gang Ji.
      It has been reported that miR-217 can inhibit the oncogenic activity and progression of bladder cancer (BCa) cells, but it has not been explored whether miR-217 is involved in the regulation of ferroptosis. In the present study, RNA transfection, real-time PCR, flow cytometry, Western blotting assays, immunofluorescence and ELISA were performed to explore the effects and mechanisms of miR-217 in BCa tissue-derived exosomes. We found that extracellular fluid from bladder cancer tissue promoted the growth and miR-217 expression of T24 cells and inhibited ferroptosis. MiR-217 was confirmed to inhibit ferroptosis in bladder cancer cells by RNA interference and functional assays. By cell membrane fluorescence probe (CM-Dil) labeling, inhibiting exosome secretion by GW4689 and exosome extraction, we determined that BCa tissue-derived exosomes transport miR-217 into T24 cells. Culture of T24 cells with extracellular fluid after RNA interference showed that exosomes carrying miR-217 derived from BCa tissues inhibited ferroptosis of T24 cells. We conclude that bladder cancer tissue-derived exosomes inhibit ferroptosis of T24 bladder cancer cells by transporting miR-217. The results of our study provide a new insight into the progression of bladder cancer.
    Keywords:  Exosomes; bladder cancer; ferroptosis; miR-217
    DOI:  https://doi.org/10.1002/em.22520
  3. Methods Mol Biol. 2023 ;2595 13-47
    Exosomal MicroRNA Profiling.
    Neda Rahimian, Javid Sadri Nahand, Michael R Hamblin, Hamed Mirzaei.
      Exosomes are extracellular vesicles, which have the ability to convey various types of cargo between cells. Lately, a great amount of interest has been paid to exosomal microRNAs (miRNAs), since much evidence has suggested that the sorting of miRNAs into exosomes is not an accidental process. It has been shown that exosomal miRNAs (exo-miRNAs) are implicated in a variety of cellular processes including (but not limited to) cell migration, apoptosis, proliferation, and autophagy. Exosomes can play a role in cardiovascular diseases and can be used as diagnostic biomarkers for several diseases, especially cancer. Tremendous advances in technology have led to the development of various platforms for miRNA profiling. Each platform has its own limitations and strengths that need to be understood in order to use them properly. In the current review, we summarize some exo-miRNAs that are relevant to exo-miRNA profiling studies and describe new methods used for the measurement of miRNA profiles in different human bodily fluids.
    Keywords:  Exosome; Isolation; MicroRNA
    DOI:  https://doi.org/10.1007/978-1-0716-2823-2_2
  4. Hematol Oncol. 2022 Nov 30.
    Using Natural Killer Cell-derived Exosomes as a Cell-Free Therapy for Leukemia.
    Aladin Samara, Michael Anbar, Saar Shapira, Anna Zemlyansky, Alla Zozovsky, Pia Raanani, Galit Granot, Uri Rozovski.
      Natural killer (NK) cells are components of the innate immune system which play a pivotal role in cancer cell surveillance. Despite promising results in clinical trials, the use of NK-based therapies is limited due to unsatisfactory efficiencies and safety issues. In recent years, exosomes have emerged as a powerful, natural therapeutic tool. Since exosomes are known to carry cargos that reflect the cellular makeup of their cell of origin, we were prompted to test whether NK-derived exosomes (NKexo) maintain the anti-leukemia capacity of NK-cells. We found NK92MI-cells to secrete large amounts of 100-200nm cap-shaped particles expressing exosomal and NK biomarkers (CD63, CD81, CD56). We demonstrated that NKexo exert a potent, selective, anti-leukemia effect on all leukemia cell-lines tested. Furthermore, NKexo eliminated leukemia cells isolated from patients with acute and chronic leukemia and inhibited hematopoietic colony growth. While leukemia cells were targeted and severely affected by NKexo, healthy B-cells remained unaffected, indicating a selective effect. This selectivity was further confirmed by demonstrating that NKexo were specifically taken up by leukemic cells but not by healthy B-cells. Our in-vivo data support our in-vitro and ex-vivo findings and demonstrate improved human-CD45+ leukemia blast counts and overall survival in NKexo treated humanized AML (HL-60) xenograft mice thus supporting the assumption that NKexo possess an anti-leukemia effect. Pending further analyses, our findings provide the pre-clinical evidence needed to test the NKexo approach in future pre-clinical and clinical studies to ultimately develop an acellular "off-the-shelf" product to treat leukemia. This article is protected by copyright. All rights reserved.
    Keywords:  Exosomes; immuno-therapy; leukemia; natural killer cells
    DOI:  https://doi.org/10.1002/hon.3111
  5. Med Oncol. 2022 Dec 02. 40(1): 31
    Exosomes: special nano-therapeutic carrier for cancers, overview on anticancer drugs.
    Leila Rezakhani, Kiavash Fekri, Gelavizh Rostaminasab, Shima Rahmati.
      Chemotherapy drugs are the first line of cancer treatment, but problems such as low intratumoral delivery, poor bioavailability, and off-site toxicity must be addressed. Cancer-specific drug delivery techniques could improve the therapeutic outcome in terms of patient survival. The current study investigated the loading of chemotherapy drugs loaded into exosomes for cancer treatment. Exosomes are the smallest extracellular vesicles found in body fluids and can be used to transfer information by moving biomolecules from cell to cell. This makes them useful as carriers. As the membranes of these nanoparticles are similar to cell membranes, they can be easily transported to carry different components. As most chemotherapy drugs are not easily soluble in liquid, loading them into exosomes can be a suitable solution to this problem. This cancer treatment could avert the injection of high doses of drugs and provide a more appropriate release mechanism.
    Keywords:  Cancer; Carrier; Chemotherapy drugs; Exosome
    DOI:  https://doi.org/10.1007/s12032-022-01887-6
  6. Front Mol Biosci. 2022 ;9 1022725
    The application of exosomes in the treatment of triple-negative breast cancer.
    John W Weaver, Jinyu Zhang, Juan Rojas, Phillip R Musich, Zhiqiang Yao, Yong Jiang.
      Triple-negative breast cancer (TNBC) is a heterogeneous and invasive breast cancer (BC) subtype that is estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2 (Her2)-negative. So far, the treatment of TNBC is still ineffective due to the lack of well-defined molecular targets. Exosomes are nanosized extracellular vesicles composed of lipid bilayers. They originate from various types of donor cells and release a complex mixture of contents including diverse nucleic acid types (miRNA, LnRNA, siRNA, and DNA) and proteins; after binding to recipient cells the exosomes release their contents that execute their biological functions. Exosomes have been reported to play an important role in the tumorigenesis of TNBC, including tumor initiation, metastasis, angiogenesis, cell proliferation, immune escape, and drug resistance. On the other hand, exosomes can be valuable biomarkers for diagnosis, monitoring, and treatment of TNBC. More interestingly, exosomes can be harnessed as a nanosized drug-delivery system specifically targeting TNBC. In this review, we present the most recent mechanistic findings and clinical applications of exosomes in TNBC therapy, focusing on their use as diagnostic and prognostic biomarkers, nanoscale drug delivery platforms, and immunotherapeutic agents. In addition, the associated challenges and future directions of using exosomes for TNBC treatment will be discussed.
    Keywords:  TNBC; biomarker; breast cancer; exosome; metastasis
    DOI:  https://doi.org/10.3389/fmolb.2022.1022725
  7. Anticancer Drugs. 2022 Nov 21.
    Exosomal miR-93-5p from cancer-associated fibroblasts confers malignant phenotypes on bladder cancer cells by targeting PAFAH1B1.
    Xiaoming Lu, Jinfeng Wang, Binbin Dong, Liping Wang, Yadong Liu.
       BACKGROUND: Dysregulation of cancer-associated fibroblasts (CAFs) still greatly challenges the treatments for bladder cancer (BC), where exosomal miRNAs derived from CAFs are one of the essential effectors for tumor progression. miR-93-5p is reported to be upregulated in BC, however, it is barely investigated in BC-derived CAFs.
    METHOD: The CAF markers were immunofluorescent-labeled and examined by western blotting assay in CAFs and normal fibroblasts (NFs). CAFs- and NFs-derived exosomes (CAFs-exo/NFs-exo) were authenticated by transmission electron microscope and nanoparticle tracking analysis. Cell viability was determined by cell counting kit-8 assay, and cell mobility was evaluated by wound healing and transwell assays. Real-time quantitative PCR was used to quantify the RNA expressions, and a western blotting assay was used for protein expression. Interaction between miR-93-5p and Platelet-Activating Factor Acetylhydrolase IB Subunit Beta (PAFAH1B1) was verified by luciferase reporter assay. HE staining assay was applied to assess the histological changes of xenografts.
    RESULTS: CAFs-exo notably enhanced cell mobility and the expression levels of miR-93-5p of BC cells compared to NFs-exo. However, inhibition of miR-93-5p in CAFs-exo exhibited attenuated pro-metastatic ability on BC cells. PAFAH1B1 was one of the predicted targets of miR-93-5p, whose mRNA level was most significantly downregulated after miR-93-5p transfection. The interaction between PAFAH1B1 and miR-93-5p was verified, and miR-93-5p negatively regulated the protein level of PAFAH1B1. Overexpression of PAFAH1B1 could efficiently reverse the effects of miR-93-5p mimic on BC cell mobility. Finally, inhibition of miR-93-5p was proved to impair the carcinogenic function of CAFs-exo in vivo.
    CONCLUSION: Exosomal miR-93-5p derived from CAFs confers oncogenicity on BC cells via sponging PAFAH1B1, suggesting a novel therapeutic strategy for BC.
    DOI:  https://doi.org/10.1097/CAD.0000000000001453
  8. Cell Biochem Biophys. 2022 Nov 28.
    Advances in the Biological Functions of Extracellular Vesicles and their Potential Use in Treating Oral Cancer.
    Jingwen Liu, Luyi Chai, Xia Zhang.
      Extracellular vesicles (EVs) are membranous spheroid organelles secreted by various cells during their development. Previous studies have proved that the elimination of metabolic waste products from the cells is one of the key biological functions of EVs. Besides, recent studies suggest that EVs also promote intercellular information transmission thus further regulating the external environment of cells, especially during the development of cancer. Different EVs are produced by tumor cells and tumor-related cells during the development of tumors. Based on their sources and contents, different EVs may promote the proliferation of tumor cells, interfere with the function of immune cells, or destroy normal tissue barriers. As a landmark component in the occurrence and development of tumors, EVs can be used to solve the biological behaviors that hinder tumor treatment, such as drug resistance and immune escape. Oral cancer is a highly prevalent cancer type in clinic and current therapies often fail to effectively inhibit its deterioration. Based on their essential roles in cancer development, EVs therefore possess great potential to be a target for oral cancer treatment. In this review, we focused on the origin and classification of vesicles in oral cancer tissues around the tumor microenvironment, described their biological functions, and discussed their potential for cancer treatment in combination with existing research methods. In addition, we highlighted the current challenges and recommendations of EVs for the treatment of oral cancer in clinic.
    Keywords:  Biological components; Drug resistance; Extracellular vesicles; Immune escape; Oral cancer
    DOI:  https://doi.org/10.1007/s12013-022-01120-1
  9. Mol Biotechnol. 2022 Dec 01.
    Tumor Cell-Derived Extracellular Vesicles Promote the Growth, Metastasis and Chemoresistance in Cholangiocarcinoma by Delivering microRNA-210 to Downregulate RECK.
    Yu Fu, Yahui Liu, Kai Liu, Ludong Tan.
      The development of cholangiocarcinoma (CCA) can be regulated by extracellular vesicles (EVs). In this study, we intend to investigate whether tumor cell-derived EVs delivering microRNA (miR)-210 affect CCA development, involved with reversion-inducing-cysteine-rich protein with kazal motifs (RECK). In silico analysis was performed for identifying differentially expressed miRs and the downstream target genes. The CCA related microarray GSE77984 was used to verify the expression of the target genes in CCA tissue samples. Targeting relationship between miR-210 and RECK was assayed. EVs were extracted from CCA cells, followed by co-culture with CCA cells. The in vitro and in vivo roles of tumor cell-derived EVs on the growth and metastasis of CCA cells were assayed. Upregulated miR-210 and downregulated RECK were found in CCA. CCA cells could uptake tumor cell-derived EVs, and the EVs could promote their migration, invasion, and chemoresistance. RECK expression could be target and inhibited by miR-210. It was further confirmed in vivo that miR-210 shuttled by tumor cell-derived EVs could specifically inhibit RECK expression, which promotes growth, metastasis and chemoresistance of CCA cells. Our current study highlighted that tumor cell-derived EVs could deliver miR-210 to CCA cells, where miR-210 specifically decreases RECK expression, which facilitates growth, metastasis and chemoresistance in CCA.
    Keywords:  Chemoresistance; Cholangiocarcinoma; Extracellular vesicles; RECK; Tumor growth; Tumor metastasis; microRNA-210
    DOI:  https://doi.org/10.1007/s12033-022-00607-9
  10. Kaohsiung J Med Sci. 2022 Nov 30.
    Exosomal circNFIX promotes angiogenesis in ovarian cancer via miR-518a-3p/TRIM44 axis.
    Hui Ye, Rui-Yu Wang, Xiu-Zhang Yu, Yu-Ke Wu, Bo-Wen Yang, Meng-Yin Ao, Ming-Rong Xi, Min-Min Hou.
      Ovarian cancer (OC) is a gynecological cancer with high mortality. OC-derived exosomal circRNAs can regulate angiogenesis. This study aims to explore the role and mechanism of exosomal circRNA nuclear factor I X (CircNFIX) derived from OC cells in angiogenesis. Quantitative real-time polymerase chain reaction was employed to evaluate the levels of circNFIX, miR-518a-3p, and tripartite motif protein 44 (TRIM44) in OC and adjacent tissues. Exosomes from the ovarian surface epithelial cell (HOSEpiC) and OC cells (SKOV3 or OVCAR3) were isolated by differential centrifugation. Exosomes were cocultured with the human umbilical vein endothelial cells (HUVECs). The angiogenesis capacity was analyzed by Tube formation assay. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and Transwell assays were used to determine the cell viability and migration ability. The dual-luciferase report, RNA immunoprecipitation (RIP), and RNA pull-down assays were applied to validate the gene's interaction. CircNFIX and TRIM44 expression were higher and miR-518a-3p was lower in OC tissues than in the adjacent tissues. Upregulated circNFIX and TRIM44 were significantly correlated with the tumor size and International Federation of Gynecology and Obstetrics (FIGO) stage of OC patients. HUVECs treated OC-derived exosomes had higher proliferation, migration, and angiogenesis capacities than the control group. While OC-derived exosomal circNFIX silencing restrained HUVECs' proliferation, migration, and angiogenesis, compared with the OC-derived exosomes group. OC-derived exosomal circNFIX positively regulated TRIM44 expression by targeting miR-518a-3p in HUVECs. OC-derived exosomal circNFIX promoted angiogenesis by regulating the Janus-activated kinase/signal transducer and activator of transcription 1 (JAK/STAT1) pathway via miR-518a-3p/TRIM44 axis in HUVECs.
    Keywords:  angiogenesis; circNFIX; exosomes; miR-518a-3p; ovarian cancer
    DOI:  https://doi.org/10.1002/kjm2.12615
  11. Exp Mol Med. 2022 Nov 29.
    Dissecting exosome inhibitors: therapeutic insights into small-molecule chemicals against cancer.
    Jong Hyun Kim, Chan-Hyeong Lee, Moon-Chang Baek.
      Intensive research in the field of cancer biology has revealed unique methods of communication between cells through extracellular vesicles called exosomes. Exosomes are released from a broad spectrum of cell types and serve as functional mediators under physiological or pathological conditions. Hence, blocking the release of exosome bio carriers may prove useful for slowing the progression of certain types of cancers. Therefore, efforts are being made to develop exosome inhibitors to be used both as research tools and as therapies in clinical trials. Thus, studies on exosomes may lead to a breakthrough in cancer research, for which new clinical targets for different types of cancers are urgently needed. In this review, we briefly outline exosome inhibitors and discuss their modes of action and potential for use as therapeutic tools for cancer.
    DOI:  https://doi.org/10.1038/s12276-022-00898-7
  12. Front Bioeng Biotechnol. 2022 ;10 1069676
    Colon cancer exosome-derived biomimetic nanoplatform for curcumin-mediated sonodynamic therapy and calcium overload.
    Yang Li, Chunyu Huang, Youhua Xu.
      Sonodynamic therapy (SDT) possesses unique properties such as being minimally invasive, exhibiting low toxicity, as well as ability to impart the treatment in the deep tissues, and hence has been extensively used. However, inherent defects such as low water-soluble sonosensitizers can limit the clinical application of SDT, and tumor microenvironment (TME) can further compromise the effect of a single SDT. To overcome these challenges, we have designed a bionic nano-system (ECaC) by coating mesoporous calcium carbonate nanoparticles (CaCO3 NPs) and sonosensitizer curcumin (Cur) into tumor-derived exosomes for developing enhanced SDT. Exosome membrane could endow CaCO3 NPs with homologous targeting abilities. In addition, compared with the bare CaCO3 NPs, ECaC showed significant accumulation in the tumor cell species. Subsequently, CaCO3 NPs upon reaching the tumor site can be degraded into Ca2+ in response to the acidic microenvironment of the tumor to destroy the cellular mitochondria. Hence, the cellular respiration could be destroyed to be a vulnerable state, causing oxidative stress, enhancing Cur-mediated chemotherapy/SDT. This synergistically dynamic therapy has demonstrated significant anti-tumor effects under in vitro and in vivo settings without exhibiting any toxic side effects. Our prepared biomimetic nano-system can effectively deliver the hydrophobic Cur to the tumor sites, which holds great promise in field of drug delivery and can broaden the application of exosomes, as this method has a certain enlightenment effect on the subsequent development of exosomes.
    Keywords:  calcium carbonate; curcumin; drug delivery; exosome; sonodynamic therapy
    DOI:  https://doi.org/10.3389/fbioe.2022.1069676
  13. Cancer Cell Int. 2022 Dec 01. 22(1): 378
    Exosomal circular RNA: a signature for lung cancer progression.
    Bashdar Mahmud Hussen, Snur Rasool Abdullah, Goran Sedeeq Hama Faraj, Mohammed Fatih Rasul, Abbas Salihi, Soudeh Ghafouri-Fard, Mohammad Taheri, Majid Mokhtari.
      Membrane vesicles having a diameter of 30-150 nm are known as exosomes. Several cancer types secrete exosomes, which may contain proteins, circular RNAs (circRNAs), microRNAs, or DNA. CircRNAs are endogenous RNAs that do not code for proteins and can create continuous and covalently closed loops. In cancer pathogenesis, especially metastasis, exosomal circRNAs (exo-circRNAs) have a crucial role mainly due to the frequently aberrant expression levels within tumors. However, neither the activities nor the regulatory mechanisms of exo-circRNAs in advancing lung cancer (LC) are obvious. A better understanding of the regulation and network connections of exo-circRNAs will lead to better treatment for LCs. The main objective of the current review is to highlight the functions and mechanisms of exo-circRNAs in LC and assess the relationships between exo-circRNA dysregulation and LC progression. In addition, underline the possible therapeutic targets based on exo-circRNA modulating.
    Keywords:  Circular RNA (circRNA); Exosomal circular RNA (exo-circRNA); Lung Cancer (LC)
    DOI:  https://doi.org/10.1186/s12935-022-02793-7
  14. Med Oncol. 2022 Dec 01. 40(1): 24
    Gastric cancer stem cell-derived exosomes promoted tobacco smoke-triggered development of gastric cancer by inducing the expression of circ670.
    Zhao Feng Liang, Yue Zhang, Wenhao Guo, Bei Chen, Shikun Fang, Hui Qian.
      As one of the most common malignant cancers in the world, gastric cancer is caused by mang factors among which tobacco smoke is an important risk factor. Gastric cancer stem cells (GCSCs) and the derived exosomes play a key role in the occurrence and development of gastric cancer, and exosomal circRNA is considered as a new regulatory factor in the development of gastric cancer. However, it is unclear whether tobacco smoke can affect exosomes and their transport circRNAs to promote the development of gastric cancer. Herein, we provided a new insight into tobacco smoke promoting the progression of gastric cancer. In the present study, we demonstrated that tobacco smoke-induced exosomes promoted the spheroidizing ability, stemness genes expression, and epithelial-mesenchymal transition (EMT) process of GCSCs. We further found that hsa-circRNA-000670 (circ670) was up-regulated in tissues of gastric cancer patients with smoking history, tobacco smoke-induced GCSCs, and their exosomes. Functional assays have shown that circ670 knockdown inhibited the stemness and EMT process of GCSCs, whereas circ670 overexpression appeared to have an opposite effect. Our findings indicated that exosomal circ670 promotes the development of tobacco smoke-induced gastric cancer, which may provide insight into the mechanism of tobacco smoke promoting the progression of gastric cancer.
    Keywords:  Exosomes; Gastric cancer; Gastric cancer stem cells; Tobacco smoke; circRNA
    DOI:  https://doi.org/10.1007/s12032-022-01906-6
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