bims-exocan 2023-12-31 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2023–12–31
nine papers selected by
Muhammad Rizwan, COMSATS University

Exosomes in lung cancer metastasis, diagnosis, and immunologically relevant advances.
Irradiated Cell-derived Exosomes Enhance Cell Proliferation and Radioresistance via the MAPK/Erk Pathway.
CAFs-derived exosomes promote the development of cervical cancer by regulating miR-18a-5p-TMEM170B signaling axis.
Engineered Exosome for Drug Delivery: Recent Development and Clinical Applications.
Gastric cancer and mesenchymal stem cell-derived exosomes: from pro-tumorigenic effects to anti-cancer vehicles.
Engineered extracellular vesicles: A new approach for targeted therapy of tumors and overcoming drug resistance.
Exosomal microRNAs: implications in the pathogenesis and clinical applications of subarachnoid hemorrhage.
Exosomes: Membrane-associated proteins, challenges and perspectives.
The emerging role of breast cancer derived extracellular vesicles-mediated intercellular communication in ovarian cancer progression and metastasis.

Front Immunol. 2023 ;14 1326667

Exosomes in lung cancer metastasis, diagnosis, and immunologically relevant advances.

Jianhua Zhao, Xiwen Li, Lele Liu, Zhen Zhu, Chunyan He.

  Lung cancer is a chronic wasting disease with insidious onset and long treatment cycle. Exosomes are specialized extracellular vesicles, at first exosomes were considered as a transporter of cellular metabolic wastes, but recently many studies have identified exosomes which contain a variety of biologically active substances that play a role in the regulation of cellular communication and physiological functions. Exosomes play an important role in the development of lung cancer and can promote metastasis through a variety of mechanisms. However, at the same time, researchers have also discovered that immune cells can also inhibit lung cancer through exosomes. In addition, researchers have discovered that some specific miRNAs in exosomes can be used as markers for early diagnosis of lung cancer. Engineering exosomes may be one of the strategies to enhance the clinical translational application of exosomes in the future, for example, strategies such as modifying exosomes to enhance targeting or utilizing exosomes as carriers for drug delivery have been explored. but more studies are needed to verify the safety and efficacy. This article reviews the latest research on exosomes in the field of lung cancer, from the mechanism of lung cancer development, the functions of immune cell-derived exosomes and tumor-derived exosomes, to the early diagnosis of lung cancer.

Keywords:  EMT; exosome; immunotherapy; lung cancer; miRNA; neovascularization

DOI:  https://doi.org/10.3389/fimmu.2023.1326667
Cancer Genomics Proteomics. 2024 Jan-Feb;21(1):21(1): 12-17

Irradiated Cell-derived Exosomes Enhance Cell Proliferation and Radioresistance via the MAPK/Erk Pathway.

Yue Dong, Keisuke Tamari, Maiko Kishigami, Shohei Katsuki, Kazumasa Minami, Shotaro Tatekawa, Shinichi Shimizu, Masahiko Koizumi, Kazuhiko Ogawa.

   BACKGROUND/AIM: Radiation therapy is pivotal in cancer treatment; however, its efficacy is limited by challenges such as tumor recurrence. This study delves into the role of exosomes, which are molecular cargo-bearing vesicles, in influencing cell proliferation, radioresistance, and consequent post-irradiation tumor recurrence. Given the significance of exosomes from irradiated malignancies in diagnostics and therapy, it is vital to delineate their functional dynamics, especially in breast and cervical cancer cell lines, where the impact of irradiation on exosome behavior remains enigmatic.
MATERIALS AND METHODS: Using MDA-MB-231 and HeLa cell lines, exosomes were isolated from the culture supernatant via ultracentrifugation. The bicinchoninic acid assay was used to measure exosome quantities in irradiated and non-irradiated cells. Radiosensitivity was assessed using colony formation assays, while the role of the MAPK/Erk signaling pathway in recipient cell proliferation and radioresistance was probed using western blotting.
RESULTS: Irradiated cells, in both MDA-MB-231 and HeLa lines, produced significantly more exosomes than their non-irradiated counterparts. Co-culturing irradiated cells with exosomes led to increased cell survival post-irradiation and enhanced cell proliferation in both cell lines. Western blotting indicated elevated p-Erk expression in such cells, underscoring the influence of the MAPK/Erk pathway in radioresistance and proliferation.
CONCLUSION: The study establishes a potential nexus between exosome secretion and tumor resurgence following radiotherapy. The spotlight falls on the MAPK/ERK signaling conduit as a key influencer. This new knowledge provides an innovative strategy for counteracting cancer recurrence after radiotherapy, emphasizing the importance of understanding the multifaceted roles of exosomes in this context.

Keywords:  MAPK/ERK signaling; Radiation; cellular proliferation; exosome; resistance

DOI:  https://doi.org/10.21873/cgp.20425
Biochem Biophys Res Commun. 2023 Dec 22. pii: S0006-291X(23)01497-3. [Epub ahead of print]694 149403

CAFs-derived exosomes promote the development of cervical cancer by regulating miR-18a-5p-TMEM170B signaling axis.

Cong Kang, Yali Duo, Lei Zheng, Ning Zhao, Jing Wang, Zhongjie Liu, Lei Qiu, FengLing Bi.

  Mounting studies have showed that tumor microenvironment (TME) is crucial for cervical cancer (CC), and cancer-related fibroblasts (CAFs) play a major role in it. Recently, exosomal miRNAs secreted by CAFs have been found to be potential targets for cancer diagnosis and therapy. In this paper, we aimed to investigate the function of CAFs-mediated exosome miR-18a-5p (CAFs-exo-miR-18a-5p) in CC. First, in combination with bioinformatic data analysis of the GEO database (GSE86100) and RT-qPCR of CC clinical tissue samples and cell lines, miR-18a-5p was discovered to be markedly up-regulated in CC. Next, CAFs-secreted exosomes were isolated and it was found that miR-18a-5p expression was dramatically promoted in CC cell lines when treated with CAFs-exos. The CAFs-exo-miR-18a-5p was then elucidated to stimulate the proliferation and migration and inhibit the apoptosis of CC cells. In order to clarify the underlying mechanism, we further screened the target genes of miR-18a-5p. TMEM170B was selected by bioinformatic data analysis of online databases combined with RT-qPCR of CC clinical tissues and cells. Luciferase reporter gene analysis combined with molecular biology experiments further elucidated that miR-18a-5p suppressed TMEM170B expression in CC. Finally, both cell and animal experiments demonstrated that TMEM170B over-expression attenuated the oncogenic effect of CAFs-exo-miR-18a-5p. In conclusion, our study indicates that CAFs-mediated exosome miR-18a-5p promotes the initiation and development of CC by suppressing TMEM170B signaling axis, which provides a possible direction for the diagnosis and therapy of CC.

Keywords:  Cancer-related fibroblasts; Cervical cancer; Exosomes; TMEM170B; miR-18a-5p

DOI:  https://doi.org/10.1016/j.bbrc.2023.149403
Int J Nanomedicine. 2023 ;18 7923-7940

Engineered Exosome for Drug Delivery: Recent Development and Clinical Applications.

Jiaqi Tian, Zhengpu Han, Dandan Song, Yanjie Peng, Min Xiong, Zhen Chen, Shuyin Duan, Lin Zhang.

  Exosomes are nano-sized membrane vesicles that transfer bioactive molecules between cells and modulate various biological processes under physiological and pathological conditions. By applying bioengineering technologies, exosomes can be modified to express specific markers or carry therapeutic cargo and emerge as novel platforms for the treatment of cancer, neurological, cardiovascular, immune, and infectious diseases. However, there are many challenges and uncertainties in the clinical translation of exosomes. This review aims to provide an overview of the recent advances and challenges in the translation of engineered exosomes, with a special focus on the methods and strategies for loading drugs into exosomes, the pros and cons of different loading methods, and the optimization of exosome production based on the drugs to be encapsulated. Moreover, we also summarize the current clinical applications and prospects of engineered exosomes, as well as the potential risks and limitations that need to be addressed in exosome engineering, including the standardization of exosome preparation and engineering protocols, the quality and quantity of exosomes, the control of drug release, and the immunogenicity and cytotoxicity of exosomes. Overall, engineered exosomes represent an exciting frontier in nanomedicine, but they still face challenges in large-scale production, the maintenance of storage stability, and clinical translation. With continuous advances in this field, exosome-based drug formulation could offer great promise for the targeted treatment of human diseases.

Keywords:  clinical application; drug delivery; engineered exosomes; preparation strategy

DOI:  https://doi.org/10.2147/IJN.S444582
Arch Pharm Res. 2023 Dec 27.

Gastric cancer and mesenchymal stem cell-derived exosomes: from pro-tumorigenic effects to anti-cancer vehicles.

Maryam Dolatshahi, Ahmad Reza Bahrami, Qaiser Iftikhar Sheikh, Mohsen Ghanbari, Maryam M Matin.

  Gastric cancer (GC) is one of the most prevalent malignancies in the world, with a high mortality rate in both women and men. Conventional treatments, like chemotherapy, radiotherapy and surgery, are facing some drawbacks like acquired drug resistance and various side effects, leading to cancer recurrence and increased morbidity; thus, development of novel approaches in targeted therapy would be very beneficial. Exosomes, extracellular vesicles with a size distribution of sub-150 nm, interplay in physiological and pathophysiological cell-cell communications and can pave the way for targeted cancer therapy. Accumulating pieces of evidence have indicated that exosomes derived from mesenchymal stem cells (MSC-EXs) can act as a double-edged sword in some cancers. The purpose of this review is to assess the differences between stem cell therapy and exosome therapy. Moreover, our aim is to demonstrate how naïve MSCs transform into GC-MSCs in the tumor microenvironment. Additionally, the tumorigenic and anti-proliferation effects of MSC-EXs derived from different origins were investigated. Finally, we suggest potential modifications and combination options that involve utilizing MSC-EXs from the foreskin and umbilical cord as promising sources to enhance the efficacy of gastric cancer treatment. This approach is presented in contrast to bone marrow cells, which are more heterogeneous, age-related, and are also easily affected by the patient's circulation system.

Keywords:  Exosomes; Extracellular vesicles; Gastric cancer; Mesenchymal stem cells

DOI:  https://doi.org/10.1007/s12272-023-01477-8
Cancer Commun (Lond). 2023 Dec 28.

Engineered extracellular vesicles: A new approach for targeted therapy of tumors and overcoming drug resistance.

Chen Ming-Kun, Chen Zi-Xian, Cai Mao-Ping, Chen Hong, Chen Zhuang-Fei, Zhao Shan-Chao.

  Targeted delivery of anti-tumor drugs and overcoming drug resistance in malignant tumor cells remain significant clinical challenges. However, there are only few effective methods to address these issues. Extracellular vesicles (EVs), actively secreted by cells, play a crucial role in intercellular information transmission and cargo transportation. Recent studies have demonstrated that engineered EVs can serve as drug delivery carriers and showed promising application prospects. Nevertheless, there is an urgent need for further improvements in the isolation and purification of EVs, surface modification techniques, drug assembly processes, and precise recognition of tumor cells for targeted drug delivery purposes. In this review, we summarize the applications of engineered EVs in cancer treatment and overcoming drug resistance, and current challenges associated with engineered EVs are also discussed. This review aims to provide new insights and potential directions for utilizing engineered EVs as targeted delivery systems for anti-tumor drugs and overcoming drug resistance in the near future.

Keywords:  drug delivery; drug resistance; extracellular vesicles; nanoparticles

DOI:  https://doi.org/10.1002/cac2.12518
Front Mol Neurosci. 2023 ;16 1300864

Exosomal microRNAs: implications in the pathogenesis and clinical applications of subarachnoid hemorrhage.

Lishang Liao, Haoran Wang, Deli Wei, Mingliang Yi, Yingjiang Gu, Mingwei Zhang, Li Wang.

  Subarachnoid hemorrhage (SAH) is a severe acute neurological disorder with a high fatality rate. Early brain injury (EBI) and cerebral vasospasm are two critical complications of SAH that significantly contribute to poor prognosis. Currently, surgical intervention and interventional therapy are the main treatment options for SAH, but their effectiveness is limited. Exosomes, which are a type of extracellular vesicles, play a crucial role in intercellular communication and have been extensively studied in the past decade due to their potential influence on disease progression, diagnosis, and treatment. As one of the most important components of exosomes, miRNA plays both direct and indirect roles in affecting disease progression. Previous research has found that exosomal miRNA is involved in the development of various diseases, such as tumors, chronic hepatitis, atherosclerosis, diabetes, and SAH. This review focuses on exploring the impact of exosomal miRNA on SAH, including its influence on neuronal apoptosis, inflammatory response, and immune activation following SAH. Furthermore, this review highlights the potential clinical applications of exosomal miRNA in the treatment of SAH. Although current research on this topic is limited and the clinical application of exosomal miRNA has inherent limitations, we aim to provide a concise summary of existing research progress and offer new insights for future research directions and trends in this field.

Keywords:  apoptosis; early brain injury; exosomal micro-RNAs; immune activation; inflammatory response; subarachnoid hemorrhage

DOI:  https://doi.org/10.3389/fnmol.2023.1300864
Biochem Biophys Rep. 2024 Mar;37 101599

Exosomes: Membrane-associated proteins, challenges and perspectives.

Nuria Palomar-Alonso, Mijung Lee, Manho Kim.

  Membrane proteins determine the precise function of each membrane and, therefore, the function of each cell type. These proteins essential roles in cell physiology, participating in the maintenance of the cell metabolism, its homeostasis or promoting proper cell growth. Membrane proteins, as has long been described, are located both in the plasma membrane and in complex subcellular structures. However, they can also be released into the extracellular environment associated with extracellular vesicles (EVs). To date, most of the research have been focused on understanding the role of exosomal RNA in several processes. Recently, there has been increasing interest in studying the function of exosome membrane proteins for exosome-based therapy, but not much research has been done yet on the function of exosome membrane proteins. One of the major limitations of studying exosome membrane proteins and their application to translational research of exosome-based therapeutics is the low yield of exosome isolation. Here, we have introduced a new perspective on exosome membrane protein research by reviewing studies showing the important role of exosome membrane proteins in exosome-based therapies. Furthermore, we have proposed a new strategy to boost the yield of exosome isolation: hybridization of liposomes with exosome-derived membrane. Liposomes have already been reported to affect the cell excitation to increase exosome production in tumor cells. Therefore, increasing cellular uptake of these liposomes would enhance exosome release by increasing cellular excitation. This new perspective could be a breakthrough in exosome-based therapeutic research.

Keywords:  Exosomes; Extracellular vesicles; Liposomes; Membrane proteins

DOI:  https://doi.org/10.1016/j.bbrep.2023.101599
Med Oncol. 2023 Dec 26. 41(1): 30

The emerging role of breast cancer derived extracellular vesicles-mediated intercellular communication in ovarian cancer progression and metastasis.

Melis Rahime Yıldırım, Oğuz Kaan Kırbaş, Hüseyin Abdik, Fikrettin Şahin, Ezgi Avşar Abdik.

  Breast cancer is one of the most occurring cancer types in women worldwide and metastasizes to several organs such as bone, lungs, liver, brain, and ovaries. Extracellular vesicles (EVs) mediate intercellular signaling which has a profound effect on tumor development and metastasis. Recent developments in the field of EVs provide an opportunity to investigate the roles of EVs released from tumor cells in metastasis. In this study, we compared the effects of metastatic breast cancer-derived EVs on both nonluteinized granulosa HGrC1 and ovarian cancer OVCAR-3 cells in terms of proliferation, invasion, apoptosis, and gene expression levels. EVs were isolated from the culture medium of metastatic breast cancer cell line MDA-MB-231 by ultracentrifugation. Cell proliferation, apoptosis, cell cycle, invasion, and cellular uptake analysis were performed to clarify the roles of tumor-derived EVs in both cells. 6.85 × 108 nanoparticles of BCD-EVs were markedly increased cell proliferation as well as invasion capacity. Exposing the cells with BCD-EVs for 24 h, resulted in an accumulation of both cells in G2/M phase as determined by flow cytometry. The apoptosis assay results were consistent with cell proliferation and cell cycle results. The uptake of the BCD-EVs was efficiently internalized by both cells. In addition, marked variations in fatty acid composition between cells were observed. BCD-EVs appeared new fatty acids in HGrC1. Besides, BCD-EVs upregulated epithelial-mesenchymal transition (EMT) and proliferation-related genes. In conclusion, an environment of tumor-derived EVs changes the cellular phenotype of cancer and noncancerous cells and may lead to tumor progression and metastasis.

Keywords:  Breast cancer; Extracellular vesicles; Fatty acid profile; Invasion; Metastasis; Ovarian cancer

DOI:  https://doi.org/10.1007/s12032-023-02285-2