bims-exocan 2023-10-01 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2023–10–01
eleven papers selected by
Muhammad Rizwan, COMSATS University

An emerging research: the role of hepatocellular carcinoma-derived exosomal circRNAs in the immune microenvironment.
Revolutionizing treatment for triple-negative breast cancer: Harnessing the power of exosomal miRNAs for targeted therapy.
The role of exosomes in cancer biology by shedding light on their lipid contents.
Exosomes in the Diagnosis and Treatment of Renal Cell Cancer.
Application of cell-derived exosomes in the hematological malignancies therapy.
Communicator Extraordinaire: Extracellular Vesicles in the Tumor Microenvironment Are Essential Local and Long-Distance Mediators of Cancer Metastasis.
Exosomal non-coding RNAs: Blueprint in colorectal cancer metastasis and therapeutic targets.
SYT7 is a key player in increasing exosome secretion and promoting angiogenesis in non-small-cell lung cancer.
The Comparison of Serum Exosome Protein Profile in Diagnosis of NSCLC Patients.
Exosome Cargos as Biomarkers for Diagnosis and Prognosis of Hepatocellular Carcinoma.
Exosomes as a drug delivery tool for cancer therapy: a new era for existing drugs and oncolytic viruses.

Front Immunol. 2023 ;14 1227150

An emerging research: the role of hepatocellular carcinoma-derived exosomal circRNAs in the immune microenvironment.

Huang-Zhen Xu, Xin-Yi Lin, Yun-Xian Xu, Hui-Bin Xue, Shu Lin, Tian-Wen Xu.

  Hepatocellular carcinoma (HCC), the most common primary malignancy of the liver, is one of the leading causes of cancer-related death and is associated with a poor prognosis. The tumor microenvironment (TME) of HCC comprises immune, immunosuppressive, and interstitial cells with hypoxic, angiogenic, metabolic reprogramming, inflammatory, and immunosuppressive features. Exosomes are nanoscale extracellular vesicles that secrete biologically active signaling molecules such as deoxyribonucleic acid (DNA), messenger ribonucleic acid (mRNA), microribonucleic acid (miRNA), proteins, and lipids. These signaling molecules act as messengers in the tumor microenvironment, especially the tumor immunosuppressive microenvironment. Exosomal circRNAs reshape the tumor microenvironment by prompting hypoxic stress response, stimulating angiogenesis, contributing to metabolic reprogramming, facilitating inflammatory changes in the HCC cells and inducing tumor immunosuppression. The exosomes secreted by HCC cells carry circRNA into immune cells, which intervene in the activation of immune cells and promote the overexpression of immune checkpoints to regulate immune response, leading tumor cells to acquire immunosuppressive properties. Furthermore, immunosuppression is the final result of a combination of TME-related factors, including hypoxia, angiogenesis, metabolic reprogramming, and inflammation changes. In conclusion, exosomal circRNA accelerates the tumor progression by adjusting the phenotype of the tumor microenvironment and ultimately forming an immunosuppressive microenvironment. HCC-derived exosomal circRNA can affect HCC cell proliferation, invasion, metastasis, and induction of chemoresistance. Therefore, this review aimed to summarize the composition and function of these exosomes, the role that HCC-derived exosomal circRNAs play in microenvironment formation, and the interactions between exosomes and immune cells. This review outlines the role of exosomal circRNAs in the malignant phenotype of HCC and provides a preliminary exploration of the clinical utility of exosomal circRNAs.

Keywords:  circRNAs; exosome; hepatocellular carcinoma; immune escape; microenvironment

DOI:  https://doi.org/10.3389/fimmu.2023.1227150
Pathol Res Pract. 2023 Sep 16. pii: S0344-0338(23)00525-3. [Epub ahead of print]250 154825

Revolutionizing treatment for triple-negative breast cancer: Harnessing the power of exosomal miRNAs for targeted therapy.

Abduladheem Turki Jalil, Muhanad Tareq Jehad, Lubna R Al-Ameer, Anwar Qasim Khallawi, Israa M Essa, Muna S Merza, Rahman S Zabibah, Farah Al-Hili.

  Triple-negative breast cancer (TNBC) represents a challenging and aggressive form of breast cancer associated with limited treatment options and poor prognosis. Although chemotherapy is a primary therapeutic approach, drug resistance often hinders treatment success. However, the expanding knowledge of TNBC subtypes and molecular biology has paved the way for targeted therapies. Notably, exosomes (extracellular vesicles) have emerged as crucial carriers of tumorigenic factors involved in oncogenesis and drug resistance, facilitating cell-to-cell communication and offering potential as self-delivery systems. Among the cargo carried by exosomes, microRNAs (miRNAs) have gained attention due to their ability to mediate epigenetic changes in recipient cells upon transfer. Research has confirmed dysregulation of exosomal miRNAs in breast cancer cells compared to healthy cells, establishing them as promising biomarkers for cancer diagnosis and prognosis. In this comprehensive review, we summarize the latest research findings that underscore the diagnostic and prognostic significance of exosomal miRNAs in TNBC treatment. Furthermore, we explore contemporary therapeutic approaches utilizing these exosomal miRNAs for the benefit of TNBC patients, shedding light on potential breakthroughs in TNBC management.

Keywords:  Exosome; MiRNA; Therapy; Triple negative breast cancer

DOI:  https://doi.org/10.1016/j.prp.2023.154825
Pathol Res Pract. 2023 Sep 12. pii: S0344-0338(23)00513-7. [Epub ahead of print]250 154813

The role of exosomes in cancer biology by shedding light on their lipid contents.

Parisa Fayyazpour, Ali Fayyazpour, Khadijeh Abbasi, Yosra Vaez-Gharamaleki, Mohammad-Sadegh Soltani Zangbar, Mortaza Raeisi, Amir Mehdizadeh.

  Exosomes are extracellular bilayer membrane nanovesicles released by cells after the fusion of multivesicular bodies (MVBs) with the plasma membrane. One of the interesting features of exosomes is their ability to carry and transfer various molecules, including lipids, proteins, nucleic acids, and therapeutic cargoes among cells. As intercellular signaling organelles, exosomes participate in various signaling processes such as tumor growth, metastasis, angiogenesis, epithelial-to-mesenchymal transition (EMT), and cell physiology such as cell-to-cell communication. Moreover, these particles are considered good vehicles to shuttle vaccines and drugs for therapeutic applications regarding cancers and tumor cells. These bioactive vesicles are also rich in various lipid molecules such as cholesterol, sphingomyelin (SM), glycosphingolipids, and phosphatidylserine (PS). These lipids play an important role in the formation, release, and function of the exosomes and interestingly, some lipids are used as biomarkers in cancer diagnosis. This review aimed to focus on exosomes lipid content and their role in cancer biology.

Keywords:  Biomarkers; Cancer; Exosomes; Lipids; Microvesicles

DOI:  https://doi.org/10.1016/j.prp.2023.154813
Int J Mol Sci. 2023 Sep 20. pii: 14356. [Epub ahead of print]24(18):

Exosomes in the Diagnosis and Treatment of Renal Cell Cancer.

Stergios Boussios, Perry Devo, Iain C A Goodall, Konstantinos Sirlantzis, Aruni Ghose, Sayali D Shinde, Vasileios Papadopoulos, Elisabet Sanchez, Elie Rassy, Saak V Ovsepian.

  Renal cell carcinoma (RCC) is the most prevalent type of kidney cancer originating from renal tubular epithelial cells, with clear cell RCC comprising approximately 80% of cases. The primary treatment modalities for RCC are surgery and targeted therapy, albeit with suboptimal efficacies. Despite progress in RCC research, significant challenges persist, including advanced distant metastasis, delayed diagnosis, and drug resistance. Growing evidence suggests that extracellular vesicles (EVs) play a pivotal role in multiple aspects of RCC, including tumorigenesis, metastasis, immune evasion, and drug response. These membrane-bound vesicles are released into the extracellular environment by nearly all cell types and are capable of transferring various bioactive molecules, including RNA, DNA, proteins, and lipids, aiding intercellular communication. The molecular cargo carried by EVs renders them an attractive resource for biomarker identification, while their multifarious role in the RCC offers opportunities for diagnosis and targeted interventions, including EV-based therapies. As the most versatile type of EVs, exosomes have attracted much attention as nanocarriers of biologicals, with multi-range signaling effects. Despite the growing interest in exosomes, there is currently no widely accepted consensus on their subtypes and properties. The emerging heterogeneity of exosomes presents both methodological challenges and exciting opportunities for diagnostic and clinical interventions. This article reviews the characteristics and functions of exosomes, with a particular reference to the recent advances in their application to the diagnosis and treatment of RCC.

Keywords:  exosomes; mRNA; miRNA; renal cell cancer; tumor drug resistance; tumor microenvironment

DOI:  https://doi.org/10.3390/ijms241814356
Front Pharmacol. 2023 ;14 1263834

Application of cell-derived exosomes in the hematological malignancies therapy.

Kazem Ghaffari, Amin Moradi-Hasanabad, Ali Sobhani-Nasab, Javad Javaheri, Ali Ghasemi.

  Exosomes are small membrane vesicles of endocytic origin that are produced by both tumor and normal cells and can be found in physiological fluids like plasma and cell culture supernatants. They include cytokines, growth factors, proteins, lipids, RNAs, and metabolites and are important intercellular communication controllers in several disorders. According to a vast amount of research, exosomes could support or inhibit tumor start and diffusion in a variety of solid and hematological malignancies by paracrine signaling. Exosomes are crucial therapeutic agents for a variety of illnesses, such as cancer and autoimmune diseases. This review discusses the most current and encouraging findings from in vitro and experimental in vivo research, as well as the scant number of ongoing clinical trials, with a focus on the impact of exosomes in the treatment of malignancies. Exosomes have great promise as carriers of medications, antagonists, genes, and other therapeutic materials that can be incorporated into their core in a variety of ways. Exosomes can also alter the metabolism of cancer cells, alter the activity of immunologic effectors, and alter non-coding RNAs, all of which can alter the tumor microenvironment and turn it from a pro-tumor to an anti-tumor milieu. This subject is covered in the current review, which also looks at how exosomes contribute to the onset and progression of hematological malignancies, as well as their importance in diagnosing and treating these conditions.

Keywords:  biogenesis; cancer; exosomes; hematological; therapeutic agents

DOI:  https://doi.org/10.3389/fphar.2023.1263834
Biomedicines. 2023 Sep 14. pii: 2534. [Epub ahead of print]11(9):

Communicator Extraordinaire: Extracellular Vesicles in the Tumor Microenvironment Are Essential Local and Long-Distance Mediators of Cancer Metastasis.

Megan I Mitchell, Olivier Loudig.

  Human tumors are increasingly being described as a complex "ecosystem", that includes many different cell types, secreted growth factors, extracellular matrix (ECM) components, and microvessels, that altogether create the tumor microenvironment (TME). Within the TME, epithelial cancer cells control the function of surrounding stromal cells and the non-cellular ECM components in an intricate orchestra of signaling networks specifically designed for cancer cells to exploit surrounding cells for their own benefit. Tumor-derived extracellular vesicles (EVs) released into the tumor microenvironment are essential mediators in the reprogramming of surrounding stromal cells, which include cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), tumor-infiltrating lymphocytes (TILs), and tumor endothelial cells (TECs), which are responsible for the promotion of neo-angiogenesis, immune cell evasion, and invasion which are essential for cancer progression. Perhaps most importantly, tumor-derived EVs play critical roles in the metastatic dissemination of tumor cells through their two-fold role in initiating cancer cell invasion and the establishment of the pre-metastatic niche, both of which are vital for tumor cell migration, homing, and colonization at secondary tumor sites. This review discusses extracellular vesicle trafficking within the tumor microenvironment and pre-metastatic niche formation, focusing on the complex role that EVs play in orchestrating cancer-to-stromal cell communication in order to promote the metastatic dissemination of cancer cells.

Keywords:  biomarkers; cancer; cell-to-cell communication; extracellular vesicles; metastasis

DOI:  https://doi.org/10.3390/biomedicines11092534
Noncoding RNA Res. 2023 Dec;8(4): 615-632

Exosomal non-coding RNAs: Blueprint in colorectal cancer metastasis and therapeutic targets.

Bashdar Mahmud Hussen, Sara Tharwat Abdullah, Snur Rasool Abdullah, Yousif Mohammed Younis, Hazha Jamal Hidayat, Mohammed Fatih Rasul, Sayran Mohamadtahr.

  Colorectal cancer (CRC) is ranked as the world's third-most prevalent cancer, and metastatic CRC considerably increases cancer-related fatalities globally. A number of complex mechanisms that are strictly controlled at the molecular level are involved in metastasis, which is the primary reason for death in people with CRC. Recently, it has become clear that exosomes, which are small extracellular vesicles released by non-tumorous and tumorigenic cells, play a critical role as communication mediators among tumor microenvironment (TME). To facilitate communication between the TME and cancer cells, non-coding RNAs (ncRNAs) play a crucial role and are recognized as potent regulators of gene expression and cellular processes, such as metastasis and drug resistance. NcRNAs are now recognized as potent regulators of gene expression and many hallmarks of cancer, including metastasis. Exosomal ncRNAs, like miRNAs, circRNAs, and lncRNAs, have been demonstrated to influence a number of cellular mechanisms that contribute to CRC metastasis. However, the molecular mechanisms that link exosomal ncRNAs with CRC metastasis are not well understood. This review highlights the essential roles that exosomal ncRNAs play in the progression of CRC metastatic disease and explores the therapeutic choices that are open to patients who have CRC metastases. However, exosomal ncRNA treatment strategy development is still in its early phases; consequently, additional investigation is required to improve delivery methods and find novel therapeutic targets as well as confirm the effectiveness and safety of these therapies in preclinical and clinical contexts.

Keywords:  Exosomal ncRNAs; Metastatic CRC; Therapeutic targets

DOI:  https://doi.org/10.1016/j.ncrna.2023.09.001
Cancer Lett. 2023 Sep 27. pii: S0304-3835(23)00351-8. [Epub ahead of print] 216400

SYT7 is a key player in increasing exosome secretion and promoting angiogenesis in non-small-cell lung cancer.

Xiao Liu, Rui Li, Xiao Chen, Jie Yao, Qingxiang Wang, Jinghong Zhang, Yuanyuan Jiang, Yiqing Qu.

Lung cancer is the leading cause of cancer-related mortality, and non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. Our previous study confirmed that synaptotagmin 7 (SYT7) promoted NSCLC metastasis in vivo and in vitro. Studies have shown that SYT7 is an important regulatory molecule of exocytosis in various cells. However, the characteristics of SYT7 across cancers and the function of SYT7 in tumor exosome secretion remain unclear. In this study, we conducted systematic pancancer analyses of SYT7, namely, analyses of expression patterns, diagnostic and prognostic values, genetic alterations, methylation, immune infiltration, and potential biological pathways. Furthermore, we demonstrated that SYT7 increased the secretion of exosomes from A549 and H1299 cells, promoting the migration, proliferation, and tube formation of human umbilical vein endothelial cells (HUVECs). Notably, SYT7 promoted angiogenesis by transferring exosomes containing the molecule centrosomal protein of 55 kDa (CEP55) protein to HUVECs. The CEP55 protein levels was downregulated in STAT1 inhibitor-treating SYT7-overexpresion NSCLC cells. We further found that SYT7 activated the mTOR signaling pathway through the downstream molecule CEP55, thereby promoting the invasion and metastasis of NSCLC cells. SYT7 promoted exosome secretion by NSCLC cells through upregulating syntaxin-1a and syntaxin-3. In vivo, SYT7 promoted the tumorigenesis, angiogenesis and metastasis of A549 cells through the exosome pathway. Our study is of great importance for understanding the mechanism of tumor exosome secretion and the role of exosomes in tumor progression.

DOI: https://doi.org/10.1016/j.canlet.2023.216400
Int J Mol Sci. 2023 Sep 05. pii: 13669. [Epub ahead of print]24(18):

The Comparison of Serum Exosome Protein Profile in Diagnosis of NSCLC Patients.

Kamila Baran, Joanna Waśko, Jakub Kryczka, Joanna Boncela, Sławomir Jabłoński, Beata Kolesińska, Ewa Brzeziańska-Lasota, Jacek Kordiak.

  A thorough study of the exosomal proteomic cargo may enable the identification of proteins that play an important role in cancer development. The aim of this study was to compare the protein profiles of the serum exosomes derived from non-small lung cancer (NSCLC) patients and healthy volunteers (control) using the high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS) method to identify potentially new diagnostic and/or prognostic protein biomarkers. Proteins exclusively identified in NSCLC and control groups were analyzed using several bioinformatic tools and platforms (FunRich, Vesiclepedia, STRING, and TIMER2.0) to find key protein hubs involved in NSCLC progression and the acquisition of metastatic potential. This analysis revealed 150 NSCLC proteins, which are significantly involved in osmoregulation, cell-cell adhesion, cell motility, and differentiation. Among them, 3 proteins: Interleukin-34 (IL-34), HLA class II histocompatibility antigen, DM alpha chain (HLA-DMA), and HLA class II histocompatibility antigen, DO beta chain (HLA-DOB) were shown to be significantly involved in the cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) infiltration processes. Additionally, detected proteins were analyzed according to the presence of lymph node metastasis, showing that differences in frequency of detection of protein FAM166B, killer cell immunoglobulin-like receptor 2DL1, and olfactory receptor 52R1 correlate with the N feature according to the TNM Classification of Malignant Tumors. These results prove their involvement in NSCLC lymph node spread and metastasis. However, this study requires further investigation.

Keywords:  cancer progression biomarker; liquid biopsy; lymph node metastasis; non-small lung cancer; protein profile; serum exosome

DOI:  https://doi.org/10.3390/ijms241813669
Pharmaceutics. 2023 Sep 21. pii: 2365. [Epub ahead of print]15(9):

Exosome Cargos as Biomarkers for Diagnosis and Prognosis of Hepatocellular Carcinoma.

Yulai Zeng, Shuyu Hu, Yi Luo, Kang He.

  Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Due to the insidiousness of HCC onset and the lack of specific early-stage markers, the early diagnosis and treatment of HCC are still unsatisfactory, leading to a poor prognosis. Exosomes are a type of extracellular vesicle containing various components, which play an essential part in the development, progression, and metastasis of HCC. A large number of studies have demonstrated that exosomes could serve as novel biomarkers for the diagnosis of HCC. These diagnostic components mainly include proteins, microRNAs, long noncoding RNAs, and circular RNAs. The exosome biomarkers showed high sensitivity and high specificity in distinguishing HCC from health controls and other liver diseases, such as chronic HBV and liver cirrhosis. The expression of these biomarkers also exhibits correlations with various clinical factors such as tumor size, TMN stage, overall survival, and recurrence rate. In this review, we summarize the function of exosomes in the development of HCC and highlight their application as HCC biomarkers for diagnosis and prognosis prediction.

Keywords:  biomarker; circular RNA; exosome; hepatocellular carcinoma; long noncoding RNA; microRNA

DOI:  https://doi.org/10.3390/pharmaceutics15092365
Expert Opin Ther Targets. 2023 Sep 24. 1-10

Exosomes as a drug delivery tool for cancer therapy: a new era for existing drugs and oncolytic viruses.

Yoshihiko Kakiuchi, Shinji Kuroda, Nobuhiko Kanaya, Shunsuke Kagawa, Hiroshi Tazawa, Toshiyoshi Fujiwara.

   INTRODUCTION: Exosomes are cell-derived nanovesicles involved in cell-to-cell communications. These nanovesicles are generally considered to contain important carriers of information such as DNA and RNA, and show specific tropism.
AREAS COVERED: The combination of existing therapeutic agents with exosomes enhances therapeutic effects by increasing uptake into the tumor. Induction of immunogenic cell death (ICD) may also be triggered more strongly than with the drug alone. Oncolytic viruses (OVs) are even more effective as a drug in combination with exosomes. Although OVs are more likely to cause immune activity, combination with exosomes can exert synergistic effects. OVs have potent anti-tumor effects, but many limitations, such as being limited to local administration and vulnerability to attack by antibodies. Incorporation into exosomes can overcome these limitations and may allow effects against distant tumors.
EXPERT OPINION: Novel therapies using exosomes are very attractive in terms of enhancing therapeutic efficacy and reducing side effects. This approach also contains elements overcoming disadvantages in OVs, which have not been used clinically until now, and may usher in a new era of cancer treatments.

Keywords:  Cancer therapy; chemotherapy; drug delivery system; exosome; extracellular vesicle; oncolytic virus

DOI:  https://doi.org/10.1080/14728222.2023.2259102