bims-exocan 2024-04-07 papers

Issue of 2024–04–07
seven papers selected by
Muhammad Rizwan, COMSATS University

Biochem Biophys Rep. 2024 Jul;38 101695

Advances and challenges of exosome-derived noncoding RNAs for hepatocellular carcinoma diagnosis and treatment.

Min Shi, Jun-Su Jia, Guo-Sheng Gao, Xin Hua.

Exosomes, also termed extracellular vesicles (EVs), are an important component of the tumor microenvironment (TME) and exert versatile effects on the molecular communications in the TME of hepatocellular carcinoma (HCC). Exosome-mediated intercellular communication is closely associated with the tumorigenesis and development of HCC. Exosomes can be extracted through ultracentrifugation and size exclusion, followed by molecular analysis through sequencing. Increasing studies have confirmed the important roles of exosome-derived ncRNAs in HCC, including tumorigenesis, progression, immune escape, and treatment resistance. Due to the protective membrane structure of exosomes, the ncRNAs carried by exosomes can evade degradation by enzymes in body fluids and maintain good expression stability. Thus, exosome-derived ncRNAs are highly suitable as biomarkers for the diagnosis and prognostic prediction of HCC, such as exosomal miR-21-5p, miR-221-3p and lncRNA-ATB. In addition, substantial studies revealed that the up-or down-regulation of exosome-derived ncRNAs had an important impact on HCC progression and response to treatment. Exosomal biomarkers, such as miR-23a, lncRNA DLX6-AS1, miR-21-5p, lncRNA TUC339, lncRNA HMMR-AS1 and hsa_circ_0004658, can reshape immune microenvironment by regulating M2-type macrophage polarization and then promote HCC development. Therefore, by controlling exosome biogenesis and modulating exosomal ncRNA levels, HCC may be inhibited or eliminated. In this current review, we summarized the recent findings on the role of exosomes in HCC progression and analyzed the relationship between exosome-derived ncRNAs and HCC diagnosis and treatment.

Keywords: Diagnostic and therapeutic biomarkers; Exosome; Hepatocellular carcinoma; ncRNA

DOI: https://doi.org/10.1016/j.bbrep.2024.101695

Clin Transl Med. 2024 Apr;14(4): e1645

Engineering exosomes to reshape the immune microenvironment in breast cancer: Molecular insights and therapeutic opportunities.

Jilong Cao, Gang Lv, Fang Wei.

BACKGROUND: Breast cancer remains a global health challenge, necessitating innovative therapeutic approaches. Immunomodulation and immunotherapy have emerged as promising strategies for breast cancer treatment. Engineered exosomes are the sort of exosomes modified with surface decoration and internal therapeutic molecules. Through suitable modifications, engineered exosomes exhibit the capability to overcome the limitations associated with traditional therapeutic approaches. This ability opens up novel avenues for the development of more effective, personalized, and minimally invasive interventions.
MAIN BODY: In this comprehensive review, we explore the molecular insights and therapeutic potential of engineered exosomes in breast cancer. We discuss the strategies employed for exosome engineering and delve into their molecular mechanisms in reshaping the immune microenvironment of breast cancer.
CONCLUSIONS: By elucidating the contribution of engineered exosomes to breast cancer immunomodulation, this review underscores the transformative potential of this emerging field for improving breast cancer therapy.
HIGHLIGHTS: Surface modification of exosomes can improve the targeting specificity. The engineered exosome-loaded immunomodulatory cargo regulates the tumour immune microenvironment. Engineered exosomes are involved in the immune regulation of breast cancer.

Keywords: breast cancer; engineered exosomes; immune microenvironment; immunomodulation; immunotherapy

DOI: https://doi.org/10.1002/ctm2.1645

ACS Appl Bio Mater. 2024 Apr 03.

Stem Cell-Derived Exosomes: An Advanced Horizon to Cancer Regenerative Medicine.

Aparna Ramachandran, Rajib Dhar, Arikketh Devi.

Cancer research has made significant progress in recent years, and extracellular vesicles (EVs) based cancer investigation reveals several facts about cancer. Exosomes are a subpopulation of EVs. In the present decade, exosomes is mostly highlighted for cancer theranostic research. Tumor cell derived exosomes (TEXs) promote cancer but there are multiple sources of exosomes that can be used as cancer therapeutic agents (plant exosomes, stem cell-derived exosomes, modified or synthetic exosomes). Stem cells based regenerative medicine faces numerous challenges, such as promote tumor development, cellular reprogramming etc., and therefore addressing these complications becomes essential. Stem cell-derived exosomes serves as an answer to these problems and offers a better solution. Global research indicates that stem cell-derived exosomes also play a dual role in the cellular system by either inhibiting or promoting cancer. Modified exosomes which are genetically engineered exosomes or surface modified exosomes to increase the efficacy of the therapeutic properties can also be considered to target the above concerns. However, the difficulties associated with the exosomes include variations in exosomes heterogenity, isolation protocols, large scale production, etc., and these have to be managed effectively. In this review, we explore exosomes biogenesis, multiple stem cell-derived exosome sources, drug delivery, modified stem cells exosomes, clinical trial of stem cells exosomes, and the related challenges in this domain and future orientation. This article may encourage researchers to explore stem cell-derived exosomes and develop an effective and affordable cancer therapeutic solution.

Keywords: Stem cell-derived exosomes; cancer; drug delivery; mesenchymal stem cells; metastasis; therapeutic

DOI: https://doi.org/10.1021/acsabm.4c00089

World J Gastrointest Oncol. 2024 Mar 15. 16(3): 630-642

Roles and application of exosomes in the development, diagnosis and treatment of gastric cancer.

Xiao-Li Guan, Xiao-Ying Guan, Zheng-Yi Zhang.

As important messengers of intercellular communication, exosomes can regulate local and distant cellular communication by transporting specific exosomal contents and can also promote or suppress the development and progression of gastric cancer (GC) by regulating the growth and proliferation of tumor cells, the tumor-related immune response and tumor angiogenesis. Exosomes transport bioactive molecules including DNA, proteins, and RNA (coding and noncoding) from donor cells to recipient cells, causing reprogramming of the target cells. In this review, we will describe how exosomes regulate the cellular immune response, tumor angiogenesis, proliferation and metastasis of GC cells, and the role and mechanism of exosome-based therapy in human cancer. We will also discuss the potential application value of exosomes as biomarkers in the diagnosis and treatment of GC and their relationship with drug resistance.

Keywords: Cancer therapy; Diagnosis; Exosomes; Gastric cancer; Immune regulation

DOI: https://doi.org/10.4251/wjgo.v16.i3.630

BMC Cancer. 2024 Apr 01. 24(1): 400

Cancer-associated fibroblasts drive colorectal cancer cell progression through exosomal miR-20a-5p-mediated targeting of PTEN and stimulating interleukin-6 production.

Mahsa Ghofrani-Shahpar, Katayoon Pakravan, Ehsan Razmara, Faezeh Amooie, Mojdeh Mahmoudian, Masoumeh Heshmati, Sadegh Babashah.

BACKGROUND: This study evaluated the clinical relevance of a set of five serum-derived circulating microRNAs (miRNAs) in colorectal cancer (CRC). Additionally, we investigated the role of miR-20a-5p released by exosomes derived from cancer-associated fibroblasts (CAFs) in the context of CRC.
METHODS: The expression levels of five circulating serum-derived miRNAs (miR-20a-5p, miR-122-5p, miR-139-3p, miR-143-5p, and miR-193a-5p) were quantified by real-time quantitative PCR (RT-qPCR), and their associations with clinicopathological characteristics in CRC patients were assessed. The diagnostic accuracy of these miRNAs was determined through Receiver Operating Characteristic (ROC) curve analysis. CAFs and normal fibroblasts (NFs) were isolated from tissue samples, and subsequently, exosomes derived from these cells were isolated and meticulously characterized using electron microscopy and Western blotting. The cellular internalization of fluorescent-labeled exosomes was visualized by confocal microscopy. Gain- and loss-of-function experiments were conducted to elucidate the oncogenic role of miR-20a-5p transferred by exosomes derived from CAFs in CRC progression. The underlying mechanisms were uncovered through luciferase reporter assay, Western blotting, enzyme-linked immunosorbent assays, as well as proliferation and migration assays.
RESULTS: The expression levels of serum-derived circulating miR-20a-5p and miR-122-5p were significantly higher in CRC and were positively correlated with advanced stages of tumorigenesis and lymph node metastasis (LNM). In contrast, circulating miR-139-3p, miR-143-5p, and miR-193a-5p were down-regulated in CRC and associated with early tumorigenesis. Except for miR-139-3p, they showed a negative correlation with LNM status. Among the candidate miRNAs, significantly elevated levels of miR-20a-5p were observed in both cellular and exosomal fractions of CAFs. Our findings indicated that miR-20a-5p induces the expression of EMT markers, partly by targeting PTEN. Exosomal miR-20a secreted by CAFs emerged as a key factor enhancing the proliferation and migration of CRC cells. The inhibition of miR-20a impaired the proliferative and migratory potential of CAF-derived exosomes in SW480 CRC cells, suggesting that the oncogenic effects of CAF-derived exosomes are mediated through the exosomal transfer of miR-20a. Furthermore, exosomes originating from CAFs induced increased nuclear translocation of the NF-kB p65 transcription factor in SW480 CRC cells, leading to increased interleukin-6 (IL-6) production.
CONCLUSIONS: We established a set of five circulating miRNAs as a non-invasive biomarker for CRC diagnosis. Additionally, our findings shed light on the intricate mechanisms underpinning the oncogenic impacts of CAF-derived exosomes and underscore the pivotal role of miR-20a-5p in CRC progression.

Keywords: Cancer-associated fibroblasts; Colorectal cancer; Diagnosis; Exosomes; microRNA

DOI: https://doi.org/10.1186/s12885-024-12190-0

Mol Cancer. 2024 04 01. 23(1): 67

Cancer-derived exosomes as novel biomarkers in metastatic gastrointestinal cancer.

Danyang Zhong, Ziyuan Wang, Zhichao Ye, Yifan Wang, Xiujun Cai.

Gastrointestinal cancer (GIC) is the most prevalent and highly metastatic malignant tumor and has a significant impact on mortality rates. Nevertheless, the swift advancement of contemporary technology has not seamlessly aligned with the evolution of detection methodologies, resulting in a deficit of innovative and efficient clinical assays for GIC. Given that exosomes are preferentially released by a myriad of cellular entities, predominantly originating from neoplastic cells, this confers exosomes with a composition enriched in cancer-specific constituents. Furthermore, exosomes exhibit ubiquitous presence across diverse biological fluids, endowing them with the inherent advantages of non-invasiveness, real-time monitoring, and tumor specificity. The unparalleled advantages inherent in exosomes render them as an ideal liquid biopsy biomarker for early diagnosis, prognosticating the potential development of GIC metastasis.In this review, we summarized the latest research progress and possible potential targets on cancer-derived exosomes (CDEs) in GIC with an emphasis on the mechanisms of exosome promoting cancer metastasis, highlighting the potential roles of CDEs as the biomarker and treatment in metastatic GIC.

Keywords: Biomarker; Exosomes; Gastrointestinal cancer; Metastasis

DOI: https://doi.org/10.1186/s12943-024-01948-6

Heliyon. 2024 Apr 15. 10(7): e28148

Role of exosomes in the communication and treatment between OSCC and normal cells.

Xingyue Ma, Ruisi Yang, Haiyang Li, Xiaoyan Zhang, Xiao Zhang, Xiangjun Li.

Oral squamous cell carcinoma (OSCC) is a prevalent cancer that needs new therapeutic targets due to the poor postoperative prognosis in patients. Exosomes are currently one of important research areas owing to their unique properties. Exosomes are capable of acting as drug transporters, as well as facilitating interactions between OSCC and normal cells. Exosomes can be detected in body fluids such as blood, urine, cerebrospinal fluid, and bile. When exosomes are released from donor cells, they can carry various bioactive molecules to recipient cells, where these molecules participate in biological processes. This review highlights the mechanisms of exosome transfer between normal and OSCC cells. Exosomes isolated from donor OSCC cells can carry circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs) and play a role in signaling processes in the recipient OSCC cells, human umbilical vein endothelial cells, and macrophages. Exosomes secreted by carcinoma-associated fibroblasts, macrophages, and stem cells can also enter the recipient OSCC cells and modulate signaling events in these cells. Exosomes isolated from OSCC plasma, serum, and saliva are also associated with OSCC prognosis. Furthermore, while exosomes were shown to be associated with chemotherapy resistance in OSCC, they can also be used for drug delivery during OSCC treatment. In this paper, we reviewed the molecular mechanisms and functions of exosomes from different cell sources in OSCC cells, providing a basis for diagnosis and prognosis prediction in OSCC patients, and offering guidance for the design of molecular targets carried by exosomes in OSCC.

Keywords: Cell communication; Drug therapeutic tool; Exosome; Oral squamous cell carcinoma

DOI: https://doi.org/10.1016/j.heliyon.2024.e28148