bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2024–01–28
nineteen papers selected by
Muhammad Rizwan, COMSATS University
  1. Exosomes in Cancer: Diagnostic and Therapeutic Applications.
  2. A novel therapeutic strategy: the significance of exosomal miRNAs in acute myeloid leukemia.
  3. Tumor Cell-Derived Exosomal miR-191-5p Activates M2-Subtype Macrophages Through SOCS3 to Facilitate Breast Cancer.
  4. Cellular and Exosomal MicroRNAs: Emerging Clinical Relevance as Targets for Breast Cancer Diagnosis and Prognosis.
  5. METTL3-mediated HSPA9 m6A modification promotes malignant transformation and inhibits cellular senescence by regulating exosomal mortalin protein in cervical cancer.
  6. The Diagnostic and Prognostic Value of Plasmatic Exosome Count in Cancer Patients and in Patients with Other Pathologies.
  7. The role of extracellular vesicles in cholangiocarcinoma tumor microenvironment.
  8. Tumor cells-derived extracellular vesicles carry circ_0064516 competitively inhibit microRNA-6805-3p and promote cervical cancer angiogenesis and tumor growth.
  9. Exo70 Promotes the Invasion of Pancreatic Cancer Cells via the Regulation of Exosomes.
  10. Exosome: From biology to drug delivery.
  11. Exosomal microRNA-92b Is a Diagnostic Biomarker in Breast Cancer and Targets Survival-Related MTSS1L to Promote Tumorigenesis.
  12. Effective extracellular vesicles in glioma: Focusing on effective ncRNA exosomes and immunotherapy methods for treatment.
  13. Extracellular Vesicles and Exosomes: Novel Insights and Perspectives on Lung Cancer from Early Detection to Targeted Treatment.
  14. Exosome-mediated tumor metastasis: Biology, molecular targets and immuno-therapeutic options.
  15. An Update of Extracellular Vesicle Involvement in different Steps of Cancer Metastasis and Targeting Strategies.
  16. Synergistic Viro-chemoimmunotherapy in Breast Cancer Enabled by Bioengineered Immunostimulatory Exosomes and Dual-Targeted Coxsackievirus B3.
  17. Roles of Mesenchymal Stem Cells in Breast Cancer Therapy: Engineered Stem Cells and Exosomal Cell-Free Based Therapy.
  18. Exosomes from ectopic endometrial stromal cells promote M2 macrophage polarization by delivering miR-146a-5p.
  19. The potential applications of artificially modified exosomes derived from mesenchymal stem cells in tumor therapy.
  1. Clin Med Insights Oncol. 2024 ;18 11795549231215966
    Exosomes in Cancer: Diagnostic and Therapeutic Applications.
    Quratulain Maqsood, Aleena Sumrin, Yasar Saleem, Abdul Wajid, Muhammada Mahnoor.
      Small extracellular vesicles called exosomes are produced by cells and contain a range of biomolecules, including proteins, lipids, and nucleic acids. Exosomes have been implicated in the development and spread of cancer, and recent studies have shown that their contents may be exploited as biomarkers for early detection and ongoing surveillance of the disease. In this review article, we summarize the current knowledge on exosomes as biomarkers of cancer. We discuss the various methods used for exosome isolation and characterization, as well as the different types of biomolecules found within exosomes that are relevant for cancer diagnosis and prognosis. We also highlight recent studies that have demonstrated the utility of exosomal biomarkers in different types of cancer, such as lung cancer, breast cancer, and pancreatic cancer. Overall, exosomes show great promise as noninvasive biomarkers for cancer detection and monitoring. Exosomes have the ability to transform cancer diagnostic and therapeutic paradigms, providing promise for more efficient and individualized. This review seeks to serve as an inspiration for new ideas and research in the never-ending fight against cancer. Moreover, further studies are needed to validate their clinical utility and establish standardized protocols for their isolation and analysis. With continued research and development, exosomal biomarkers have the potential to revolutionize cancer diagnosis and treatment.
    Keywords:  Exosomes; biomarker; cancer; diagnosis; therapeutics
    DOI:  https://doi.org/10.1177/11795549231215966
  2. Med Oncol. 2024 Jan 23. 41(2): 62
    A novel therapeutic strategy: the significance of exosomal miRNAs in acute myeloid leukemia.
    Ali Salehi.
      Acute myeloid leukemia (AML) is a fast-growing blood cancer that interferes with the normal growth of blood cells in the bone marrow and blood. It is characterized by its unpredictable outlook and high death rate. The main treatment for AML is chemotherapy, but this often results in drug resistance and the possibility of the disease returning. For this reason, new biomarkers are necessary to diagnose, predict, and treat this disease. Research has demonstrated that cells responsible for AML release exosomes that interact with the disease's microenvironment. These exosomes have significant roles in promoting leukemia growth, suppressing normal hematopoiesis, facilitating angiogenesis, and contributing to drug resistance in AML. Further investigations have shown that these exosomes contain miRNAs, which are transferred to target cells and have functional roles. Biomarkers are utilized to assess various aspects of tumor cell behavior, including proliferation, apoptosis, angiogenesis, changes in the microenvironment, transfer of drug resistance, and stability in serum and blood plasma. In this research, we showed that exosomal miRNAs and exosomes have the potential to be used as indicators for detecting various phases of AML and can aid in its medical treatment. Furthermore, they can be specifically targeted for therapeutic purposes in addressing this condition.
    Keywords:  Acute myeloid leukemia; Exosome; MiRNA; Microenvironment; Pathogenesis
    DOI:  https://doi.org/10.1007/s12032-023-02286-1
  3. Mol Biotechnol. 2024 Jan 25.
    Tumor Cell-Derived Exosomal miR-191-5p Activates M2-Subtype Macrophages Through SOCS3 to Facilitate Breast Cancer.
    Jun Ni, Xun Xi, Sujian Xiao, Xigang Xiao.
      Differential activation of macrophages is associated with poor progression of breast cancer (BC). Many reports have elucidated the important involvement of exosomes produced by cancer cells in remodeling the macrophage activation phenotype to promote tumor expansion and invasion. However, the underlying mechanisms by which exosomes secreted by BC cells facilitate macrophage M2 polarization remain enigmatic and worth exploring. In this study, quantitative real-time PCR (RT-qPCR) was used to investigate miR-191-5p expression in BC tumor tissues and cells. Cell counting kit 8 (CCK-8), transwell, and flow cytometry were applied to assess the functional role of miR-191-5p in BC. Isolated nano-vesicles were identified using transmission electron microscopy and western blotting. We also observed that miR-191-5p was significantly elevated in BC clinical samples and that inhibition of miR-191-5p hindered the growth and metastasis of BC cells. Importantly, BC cells successfully accelerated macrophage M2-like polarization by directly transferring exosomes to macrophages, resulting in increased miR-191-5p levels in macrophages. Mechanistically, exosomal miR-191-5p directly inhibited the suppressors of cytokine signaling 3 (SOCS3) expression in macrophages and aggravated macrophage M2 polarization. Similarly, si-SOCS3 transfected macrophages boosted BC cell migration and invasion in a positive feedback manner. Overall, our results manifested a pro-growth and pro-metastatic role between the two cells by elucidating the crucial role of exosomal miR-191-5p in stimulating M2 macrophage polarization and mediating communication between BC cells and macrophages. These findings opened up new horizons for the development of BC therapeutic strategies.
    Keywords:  Breast cancer; Exosomes; M2 macrophage polarization; Nano-vesicles; SOCS3; miR-191-5p
    DOI:  https://doi.org/10.1007/s12033-023-01034-0
  4. Adv Biol (Weinh). 2024 Jan 22. e2300532
    Cellular and Exosomal MicroRNAs: Emerging Clinical Relevance as Targets for Breast Cancer Diagnosis and Prognosis.
    Faith Mokobi Zablon, Parth Desai, Kristen Dellinger, Shyam Aravamudhan.
      Breast cancer accounts for the highest cancer cases globally, with 12% of occurrences progressing to metastatic breast cancer with a low survival rate and limited effective early intervention strategies augmented by late diagnosis. Moreover, a low concentration of prognostic and predictive markers hinders disease monitoring. Circulating and exosomal microRNAs (miRNAs) have recently shown a considerable interplay in breast cancer, standing out as effective diagnostic and prognostic markers. The primary functions are as gene regulatory agents at the genetic and epigenetic levels. An array of dysregulated miRNAs stimulates cancer-promoting mechanisms, activating oncogenes and controlling tumor-suppressing genes and mechanisms. Exosomes are vastly studied extracellular vesicles, carrying, and transporting cargo, including noncoding RNAs with premier roles in oncogenesis. Translocation of miRNAs from the circulation to exosomes, with RNA-binding proteins in stress-induced conditions, has shown significant cooperation in function to promote breast cancer. This review examines cellular and exosomal miRNA biogenesis and loading, the clinical implications of their dysregulation, their function in diagnosis, prognosis, and prediction of breast cancer, and in regulating cancer signaling pathways. The influence of cellular and exosomal miRNAs presents clinical significance on breast cancer diagnosis, subtyping, staging, prediction, and disease monitoring during treatment, hence a potent marker for breast cancer.
    Keywords:  biomarker; diagnosis; exosomal miRNAs; exosomes; microRNA (miRNA); prognosis
    DOI:  https://doi.org/10.1002/adbi.202300532
  5. Cancer Lett. 2024 Jan 20. pii: S0304-3835(24)00052-1. [Epub ahead of print] 216658
    METTL3-mediated HSPA9 m6A modification promotes malignant transformation and inhibits cellular senescence by regulating exosomal mortalin protein in cervical cancer.
    Keyi Ao, Minuo Yin, Xiaoming Lyu, Yue Xiao, Xiaona Chen, Sheng Zhong, Xiuli Wen, Jianli Yuan, Ming Ye, Jiaming Zhang, Xin Li, Yi Hao, Xia Guo.
      The role of RNA methyltransferase 3 (METTL3) in tumor progression when tethered to aberrantly expressed oncogenes remains unknown. In especial, the correlation between cervical cancer (CCa)-derived exosomes and m6A methylation in malignant traits of cervical epithelium is currently elusive. Mortalin expression was found to be up-regulated in plasma exosomes isolated from CCa patients. Furthermore, mortalin gained increased mRNA stability and enhanced translation efficiency via the m6A methylation in the HSPA9 mRNA 3'UTR, which was catalysed by METTL3 in CCa cells. Exosomal mortalin overexpression significantly promoted the proliferation, migration and invasion of CCa both in vitro and in vivo. Additionally, exosome-encapsulated mortalin suppressed cellular senescence and facilitated malignant transformation by blocking nuclear transport of p53, thereby preventing the p53-Gadd45A interaction and resulting in inactivation of p53. Our studies demonstrated the significant role of METTL3 mediated exosomal mortalin in malignant transformation and cellular senescence suppression of CCa. Exosomal mortalin could clinically serve as a potential early-diagnosis biomarker and therapeutic target for CCa given its abundance and propensity to be found.
    Keywords:  Cervical cancer; Exosomes; Malignant transformation; Mortalin (HSPA9); m6A RNA methylation
    DOI:  https://doi.org/10.1016/j.canlet.2024.216658
  6. Int J Mol Sci. 2024 Jan 15. pii: 1049. [Epub ahead of print]25(2):
    The Diagnostic and Prognostic Value of Plasmatic Exosome Count in Cancer Patients and in Patients with Other Pathologies.
    Stefano Fais, Mariantonia Logozzi.
      The extent of both scientific articles and reviews on extracellular vesicles (EVs) has grown impressively over the last few decades [...].
    DOI:  https://doi.org/10.3390/ijms25021049
  7. Front Pharmacol. 2023 ;14 1336685
    The role of extracellular vesicles in cholangiocarcinoma tumor microenvironment.
    Nuoqi Zhang, Lizhuang Shu, Zengli Liu, Anda Shi, Liming Zhao, Shaohui Huang, Guoli Sheng, Zhangdi Yan, Yan Song, Fan Huang, Yongchang Tang, Zongli Zhang.
      Cholangiocarcinoma (CCA) is a highly aggressive malignant tumor that originates from the biliary system. With restricted treatment options at hand, the challenging aspect of early CCA diagnosis leads to a bleak prognosis. Besides the intrinsic characteristics of tumor cells, the generation and progression of CCA are profoundly influenced by the tumor microenvironment, which engages in intricate interactions with cholangiocarcinoma cells. Of notable significance is the role of extracellular vesicles as key carriers in enabling communication between cancer cells and the tumor microenvironment. This review aims to provide a comprehensive overview of current research examining the interplay between extracellular vesicles and the tumor microenvironment in the context of CCA. Specifically, we will emphasize the significant contributions of extracellular vesicles in molding the CCA microenvironment and explore their potential applications in the diagnosis, prognosis assessment, and therapeutic strategies for this aggressive malignancy.
    Keywords:  EV-based therapy; cholangiocarcinoma; exosome; extracellular vesicles; tumor microenvironment
    DOI:  https://doi.org/10.3389/fphar.2023.1336685
  8. Expert Opin Ther Targets. 2024 Jan 25.
    Tumor cells-derived extracellular vesicles carry circ_0064516 competitively inhibit microRNA-6805-3p and promote cervical cancer angiogenesis and tumor growth.
    Yujue Wang, Yao Xie, Xue Wang, Nian Yang, Zhao Wu, Xun Zhang.
       BACKGROUND: The current study tried to elucidate the regulatory role of tumor cell-derived exosomes (Exos)-circ_0064516 in angiogenesis and growth of cervical cancer.
    RESEARCH DESIGN AND METHODS: Related cirRNAs and downstream target genes were identified through bioinformatics analysis. Exos were isolated from cervical cancer cell line CaSki, followed by co-cultured with human umbilical vein endothelial cells (HUVECs). Then, the roles of circ_0064516, miR-6805-3p, and MAPK1 in migration and angiogenesis of HUVECs were assayed. Furthermore, xenografted tumors were transplanted into nude mice for in vivo validation.
    RESULTS: In vitro assay validated highly expressed circ_0064516 in cervical cancer cells. Tumor cell-derived Exos carried circ_0064516 to HUVECs. circ_0064516 increased MAPK1 expression by binding to miR-6805-3p, thus enhancing migration and angiogenesis. Exos containing circ_0064516 also promoted tumorigenesis of cervical cancer cells in nude mice.
    CONCLUSIONS: We confirmed the oncogenic role of tumor cell-derived Exos carrying circ_0064516 in cervical cancer progression through miR-6805-3p/MAPK1.
    Keywords:  Angiogenesis; Cervical cancer; Huvecs; MAPK1; Tumor cell-derived exosomes; ceRNA; circ_0064516; miR-6805-3p
    DOI:  https://doi.org/10.1080/14728222.2024.2306353
  9. Cancers (Basel). 2024 Jan 12. pii: 336. [Epub ahead of print]16(2):
    Exo70 Promotes the Invasion of Pancreatic Cancer Cells via the Regulation of Exosomes.
    Jingzhou Xiang, Bowen Zheng, Lingying Zhao, Yuting He, Fanzhuoran Lou, Runyang Li, Miao Fu, Xintian Huang, Wenqing Zhang, Xiaoting Hong, Li Xiao, Tianhui Hu.
      Pancreatic cancer (PC) is an aggressive and fatal malignant tumor, and exosomes have been reported to be closely related to PC invasion and metastasis. Here we found that Exo70, a key subunit of the exocyst complex, promoted PC metastasis by regulating the secretion of tumor exosomes. Clinical sample studies showed that Exo70 was highly expressed in PC and negatively correlated with patients' survival. Exo70 promoted PC cell lines' invasion and migration. Interestingly, knockdown of Exo70, or using an Exo70 inhibitor (ES2) inhibited the secretion of tumor exosomes and increased the accumulation of cellular vesicles. Furthermore, Exo70 was found to accumulate in the exosomes, which then fused with neighboring PC cells and promoted their invasion. Moreover, Exo70 increased the expression of exosomal PD-L1, leading to the immune escape of PC cells. In vivo, knockdown of Exo70 or treatment with ES2 both decreased the tumor metastasis of PC cells in mice. This study provides new insight into the mechanism of invasion and metastasis in PC and identifies Exo70 as a potential prognostic factor and therapeutic target for PC.
    Keywords:  Exo70; exocyst; exosome; metastasis; pancreatic cancer
    DOI:  https://doi.org/10.3390/cancers16020336
  10. Drug Deliv Transl Res. 2024 Jan 22.
    Exosome: From biology to drug delivery.
    Himakshi Baruah, Anupam Sarma, Debojeet Basak, Mridusmita Das.
      In recent years, different advancements have been observed in nanosized drug delivery systems. Factors such as stability, safety and targeting efficiency cause hindrances in the clinical translation of these synthetic nanocarriers. Therefore, researchers employed endogenous nanocarriers like exosomes as drug delivery vehicles that have an inherent ability to target more efficiently after appropriate functionalization and show higher biocompatibility and less immunogenicity and facilitate penetration through the biological barriers more quickly than the other available carriers. Exosomes are biologically derived lipid bilayer-enclosed nanosized extracellular vesicles (size ranges from 30 to 150 nm) secreted from both prokaryotic and eukaryotic cells and appears significantly in the extracellular space. These EVs (extracellular vesicles) can exist in different sources, including mammals, plants and microorganisms. Different advanced techniques have been introduced for the isolation of exosomes to overcome the existing barriers present with conventional methods. Extensive research on the application of exosomes in therapeutic delivery for treating various diseases related to central nervous system, bone, cancer, skin, etc. has been employed. Several studies are on different stages of clinical trials, and many exosomes patents have been registered.
    Keywords:  Biomaterial; Exosome; Extracellular vesicles; Nanocarrier; Targeted delivery
    DOI:  https://doi.org/10.1007/s13346-024-01515-y
  11. Int J Mol Sci. 2024 Jan 20. pii: 1295. [Epub ahead of print]25(2):
    Exosomal microRNA-92b Is a Diagnostic Biomarker in Breast Cancer and Targets Survival-Related MTSS1L to Promote Tumorigenesis.
    Jung-Yu Kan, Shen-Liang Shih, Sheau-Fang Yang, Pei-Yi Chu, Fang-Ming Chen, Chung-Liang Li, Yi-Chia Wu, Yao-Tsung Yeh, Ming-Feng Hou, Chih-Po Chiang.
      Exosomal microRNAs (miRNAs) are novel, non-invasive biomarkers for facilitating communication and diagnosing cancer. However, only a few studies have investigated their function and role in the clinical diagnosis of breast cancer. To address this gap, we established a stable cell line, MDA-MB-231-CD63-RFP, and recruited 112 female participants for serum collection. We screened 88 exosomal miRNAs identified through microarray analysis of 231-CD63 and literature screening using real-time PCR; only exosomal miR-92b-5p was significantly increased in patients with breast cancer. It had a significant correlation with stage and discriminated patients from the control with an AUC of 0.787. Exosomal miR-92b-5p impacted the migration, adhesion, and spreading ability of normal human mammary epithelial recipient cells through the downregulation of the actin dynamics regulator MTSS1L. In clinical breast cancer tissue, the expression of MTSS1L was significantly inversely correlated with tissue miR-92b-5p, and high expression of MTSS1L was associated with better 10-year overall survival rates in patients undergoing hormone therapy. In summary, our studies demonstrated that exosomal miR-92b-5p might function as a non-invasive body fluid biomarker for breast cancer detection and provide a novel therapeutic strategy in the axis of miR-92b-5p to MTSS1L for controlling metastasis and improving patient survival.
    Keywords:  MTSS1L; breast cancer; exosomes; miR-92b; miRNAs
    DOI:  https://doi.org/10.3390/ijms25021295
  12. Cell Biochem Funct. 2024 Jan;42(1): e3921
    Effective extracellular vesicles in glioma: Focusing on effective ncRNA exosomes and immunotherapy methods for treatment.
    Sulieman Ibraheem Shelash Al-Hawary, Sharif Alhajlah, Bokov Dmitry Olegovich, Ahmed Hjazi, Pranchal Rajput, Saad Hayif Jasim Ali, Munther Abosoda, Ali Ihsan, Shamam Kareem Oudah, Yasser Fakri Mustafa.
      This comprehensive article explores the complex field of glioma treatment, with a focus on the important roles of non-coding RNAsRNAs (ncRNAs) and exosomes, as well as the potential synergies of immunotherapy. The investigation begins by examining the various functions of ncRNAs and their involvement in glioma pathogenesis, progression, and as potential diagnostic biomarkers. Special attention is given to exosomes as carriers of ncRNAs and their intricate dynamics within the tumor microenvironment. The exploration extends to immunotherapy methods, analyzing their mechanisms and clinical implications in the treatment of glioma. By synthesizing these components, the article aims to provide a comprehensive understanding of how ncRNAs, exosomes, and immunotherapy interact, offering valuable insights into the evolving landscape of glioma research and therapeutic strategies.
    Keywords:  glioma; immunotherapy; miRNA exosomes
    DOI:  https://doi.org/10.1002/cbf.3921
  13. Biomedicines. 2024 Jan 07. pii: 123. [Epub ahead of print]12(1):
    Extracellular Vesicles and Exosomes: Novel Insights and Perspectives on Lung Cancer from Early Detection to Targeted Treatment.
    Sana Rahimian, Hossein Najafi, Baran Afzali, Mohammad Doroudian.
      Lung cancer demands innovative approaches for early detection and targeted treatment. In addressing this urgent need, exosomes play a pivotal role in revolutionizing both the early detection and targeted treatment of lung cancer. Their remarkable capacity to encapsulate a diverse range of biomolecules, traverse biological barriers, and be engineered with specific targeting molecules makes them highly promising for both diagnostic markers and precise drug delivery to cancer cells. Furthermore, an in-depth analysis of exosomal content and biogenesis offers crucial insights into the molecular profile of lung tumors. This knowledge holds significant potential for the development of targeted therapies and innovative diagnostic strategies for cancer. Despite notable progress in this field, challenges in standardization and cargo loading persist. Collaborative research efforts are imperative to maximize the potential of exosomes and advance the field of precision medicine for the benefit of lung cancer patients.
    Keywords:  NSCLC; biomarkers; circulating exosomes; diagnosis; exosomes; lung cancer; non-invasive therapeutics; targeted drug delivery; theranostics
    DOI:  https://doi.org/10.3390/biomedicines12010123
  14. Pathol Res Pract. 2024 Jan 03. pii: S0344-0338(23)00784-7. [Epub ahead of print]254 155083
    Exosome-mediated tumor metastasis: Biology, molecular targets and immuno-therapeutic options.
    Reza Moshrefiravasjani, Amin Kamrani, Nazanin Nazari, Farzaneh Jafari, Hadi Nasiri, Rana Jahanban-Esfahlan, Morteza Akbari.
      Small extracellular vesicles called exosomes play a crucial part in promoting intercellular communication. They act as intermediaries for the exchange of bioactive chemicals between cells, released into the extracellular milieu by a variety of cell types. Within the context of cancer progression, metastasis is a complex process that plays a significant role in the spread of malignant cells from their main site of origin to distant anatomical locations. This complex process plays a key role in the domain of cancer-related deaths. In summary, the trajectory of current research in the field of exosome-mediated metastasis is characterized by its unrelenting quest for more profound understanding of the molecular nuances, the development of innovative diagnostic tools and therapeutic approaches, and the unwavering dedication to transforming these discoveries into revolutionary clinical applications. This unrelenting pursuit represents a shared desire to improve the prognosis for individuals suffering from metastatic cancer and to nudge the treatment paradigm in the direction of more effective and customized interventions.
    Keywords:  Cancer; Exosome; Immunotherapy; Metastasis
    DOI:  https://doi.org/10.1016/j.prp.2023.155083
  15. Curr Med Chem. 2024 Jan 19.
    An Update of Extracellular Vesicle Involvement in different Steps of Cancer Metastasis and Targeting Strategies.
    Keywan Mortezaee, Jamal Majidpoor.
      Cancer metastasis is the deadliest event in tumorigenesis. Despite extensive research, there are still unsolved challenges regarding early metastasis detection and targeting strategies. Extracellular vesicles (EVs) and their impact on tumorigenic-related events are in the eye of current investigations. EVs represent a plethora of biomarkers and information, and they are considered key determinants in tumor progression and for tumor prognosis and monitoring. EVs are one of the key mediators for inter-cellular communications between tumor cells and their nearby stroma. They are involved in different steps of metastasis from invasion toward formation of pre-metastatic niches (PMNs), and final growth and colonization of tumor cells in desired organ/s of the target. Membrane components of EVs and their cargo can be traced for the identification of tumor metastasis, and their targeting is a promising strategy in cancer therapy. In this review, we aimed to discuss the current understanding of EV-based metastatic predilection in cancer, providing updated information about EV involvement in different metastatic steps and suggesting some strategies to hamper this devastating condition.
    Keywords:  Extracellular vesicle (EV); cancer-associated fibroblast (CAF); exosome; metastasis; pre-metastatic niche (PMN).; transforming growth factor (TGF); tumor microenvironment (TME)
    DOI:  https://doi.org/10.2174/0109298673273299231121044055
  16. ACS Nano. 2024 Jan 26.
    Synergistic Viro-chemoimmunotherapy in Breast Cancer Enabled by Bioengineered Immunostimulatory Exosomes and Dual-Targeted Coxsackievirus B3.
    Amirhossein Bahreyni, Yasir Mohamud, Sanaz Ashraf Nouhegar, Jingchun Zhang, Honglin Luo.
      Breast cancer's immunosuppressive environment hinders effective immunotherapy, but oncolytic viruses hold promise for addressing this challenge by targeting tumor cells and altering the microenvironment. Yet, neutralizing antibodies and immune clearance impede their clinical utility. This study explored microRNA-modified coxsackievirus B3 (miR-CVB3), an innovative oncolytic virus, and its potential in breast cancer treatment. It investigated miR-CVB3's impact on immune-related proteins and utilized exosomes as both protective shields and delivery carriers. Results demonstrated miR-CVB3's capacity to reshape immune-related protein profiles toward a more immunostimulatory state and enhance exosome-mediated immune cell activation. Notably, cancer cell-released exosomes encapsulating miR-CVB3 (ExomiR-CVB3) maintained its antitumor cytotoxicity and bolstered its immunostimulatory effects. Moreover, ExomiR-CVB3 shielded miR-CVB3 from neutralizing antibodies and rapid immune clearance when it was systemically administered. Building on these findings, ExomiR-CVB3 was engineered with the AS1411 aptamer and doxorubicin (ExomiR-CVB3/DoxApt), enhancing therapeutic efficacy. This notable approach, combining genomic modification, aptamer surface decoration, and doxorubicin addition, demonstrated safe delivery of CVB3 to cancer cells. Comprehensive in vitro and in vivo analyses revealed selective breast cancer cell targeting, cell death induction, and significant immune cell infiltration within the tumor microenvironment while sparing healthy organs. In summary, this study highlights ExomiR-CVB3/DoxApt as a pioneering breast cancer treatment strategy adaptable for diverse cancer types, offering a potent and versatile approach to reshaping cancer immunotherapy.
    Keywords:  CVB3; breast cancer immunotherapy; exosomes; oncolytic virus; tumor targeting
    DOI:  https://doi.org/10.1021/acsnano.3c09491
  17. Curr Mol Med. 2024 Jan 24.
    Roles of Mesenchymal Stem Cells in Breast Cancer Therapy: Engineered Stem Cells and Exosomal Cell-Free Based Therapy.
    Mohsen Karami Fath, Seyed Sajjad Zadian, Samaneh Mohammad Bagherzadeh Torbati, Vahid Saqagandomabadi, Omid Yousefi Afshar, Mohammad Khalilzad, Sara Abedi, Afshin Moliani, Ghasem Barati.
      Breast cancer has a high prevalence among women, with a high mortality rate. The number of people who suffer from breast cancer disease is increasing, whereas metastatic cancers are mostly incurable, and existing therapies have unfavorable side effects. For an extended duration, scientists have dedicated their efforts to exploring the potential of mesenchymal stem cells (MSCs) for the treatment of metastatic cancers, including breast cancer. MSCs could be genetically engineered to boost their anticancer potency. Furthermore, MSCs can transport oncolytic viruses, suicide genes, and anticancer medicines to tumors. Extracellular vesicles (EVs) are MSC products that have attracted scientist's attention as a cell-free treatment. This study narratively reviews the current state of knowledge on engineered MSCs and their EVs as promising treatments for breast cancer.
    Keywords:  Mesenchymal stem cells; breast cancer; cancer therapy; cell therapy; cell-free therapy; extracellular vesicle; genetic modification
    DOI:  https://doi.org/10.2174/0115665240274818231207054037
  18. Int Immunopharmacol. 2024 Jan 25. pii: S1567-5769(24)00091-2. [Epub ahead of print]128 111573
    Exosomes from ectopic endometrial stromal cells promote M2 macrophage polarization by delivering miR-146a-5p.
    Jiaqi Ji, Huihua Wang, Ming Yuan, Jin Li, Xiaohong Song, Kaiqing Lin.
       BACKGROUND: Ectopic endometrial stromal cells (ESCs) and M2 macrophages co-exist in the lesions of endometriosis and participate in the occurrence and progression of endometriosis. However, the interaction between ectopic ESCs and M2-type macrophage polarization is poorly understood. This study aims to investigate the effect of exosomes released from ectopic ESCs on M2 macrophage polarization and the potential mechanism.
    METHODS: Human THP-1 monocytic cells induced macrophage differentiation (M0) and M2 polarization. Ectopic ESCs and their exosomes were used to stimulate M2 macrophages. M2 macrophage polarization was examined by detecting CD163 and ARG1 expression. Exosomal microRNAs were analyzed by small-RNA sequencing.
    RESULTS: Our in vitro results suggest that exosomes of ectopic ESCs promoted M2 macrophage polarization. Meanwhile, The miR-146a-5p level was highly increased in ectopic ESCs and their exosomes and promoted the role of exosomes in M2 macrophage polarization. As a target, TRAF6 overexpression inhibits the function of miR-146a-5p mimic on M2 macrophage polarization. In the rat model, exosomes from ectopic ESCs contribute to the development of endometriosis.
    CONCLUSIONS: It was suggested that exosomes derived from ectopic ESCs promote the M2 macrophage polarization by delivering miR-146a-5p targeting TRAF6 in the pathological process of endometriosis.
    Keywords:  Endometrial stromal cells; Endometriosis; Exosome; M2 macrophages; TRAF6; miR-146a-5p
    DOI:  https://doi.org/10.1016/j.intimp.2024.111573
  19. Front Oncol. 2023 ;13 1299384
    The potential applications of artificially modified exosomes derived from mesenchymal stem cells in tumor therapy.
    Yilin Song, Quanlin Song, Daosheng Hu, Binwen Sun, Mingwei Gao, Xiangnan Liang, Boxin Qu, Lida Suo, Zeli Yin, Liming Wang.
      Mesenchymal stem cells (MSCs) have tumor-homing ability and play critical roles in tumor treatment, but their dual influences on tumor progression limit their therapeutic applications. Exosomes derived from MSCs (MSC-exosomes) exhibit great potential in targeted tumor treatment due to their advantages of high stability, low immunogenicity, good biocompatibility, long circulation time and homing characteristics. Furthermore, the artificial modification of MSC-exosomes could amplify their advantages and their inhibitory effect on tumors and could overcome the limit of tumor-promoting effect. In this review, we summarize the latest therapeutic strategies involving artificially modified MSC-exosomes in tumor treatment, including employing these exosomes as nanomaterials to carry noncoding RNAs or their inhibitors and anticancer drugs, and genetic engineering modification of MSC-exosomes. We also discuss the feasibility of utilizing artificially modified MSC-exosomes as an emerging cell-free method for tumor treatment and related challenges.
    Keywords:   mesenchymal stem cells; anti-cancer; drug delivery; exosomes; tumor-targeted therapy
    DOI:  https://doi.org/10.3389/fonc.2023.1299384
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