bims-exocan 2024-02-11 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2024–02–11
thirteen papers selected by
Muhammad Rizwan, COMSATS University

Exosomal miR-3174 induced by hypoxia promotes angiogenesis and metastasis of hepatocellular carcinoma by inhibiting HIPK3.
Clinical significance of exosomal noncoding RNAs in hepatocellular carcinoma: a narrative review.
Macrophage-derived exosomal microRNAs promote metastasis in pancreatic ductal adenocarcinoma.
Unveiling the role of ferroptosis-associated exosomal non-coding RNAs in cancer pathogenesis.
[Hepatocellular Carcinoma-Derived Exosomes: Key Players in Intercellular Communication Within the Tumor Microenvironment].
The biological role of extracellular vesicles in gastric cancer metastasis.
Polydopamine-assisted aptamer-carrying tetrahedral DNA microelectrode sensor for ultrasensitive electrochemical detection of exosomes.
RNA Profile of Cell Bodies and Exosomes Released by Tumorigenic and Non-Tumorigenic Thyroid Cells.
Exosome-Transmitted miR-224-5p Promotes Colorectal Cancer Cell Proliferation via Targeting ULK2 in p53-Dependent Manner.
Emerging Roles of Small Extracellular Vesicles in Gastrointestinal Cancer Research and Therapy.
"Triple-Punch" Strategy Exosome-Mimetic Nanovesicles for Triple Negative Breast Cancer Therapy.
Exosomal circZNF800 Derived from Glioma Stem-like Cells Regulates Glioblastoma Tumorigenicity via the PIEZO1/Akt Axis.
Acquisition of drug resistance in endothelial cells by tumor-derived extracellular vesicles and cancer progression.

iScience. 2024 Feb 16. 27(2): 108955

Exosomal miR-3174 induced by hypoxia promotes angiogenesis and metastasis of hepatocellular carcinoma by inhibiting HIPK3.

Xiao Yang, Mingyu Wu, Xiangxu Kong, Yun Wang, Chunyang Hu, Deming Zhu, Lianbao Kong, Fei Qiu, Wangjie Jiang.

  Hepatocellular carcinoma (HCC) is a highly malignant tumor with rich blood supply. HCC-derived exosomes containing hereditary substances including microRNAs (miRNAs) were involved in regulating tumor angiogenesis and metastasis. Subsequently, series experiments were performed to evaluate the effect of exosomal miR-3174 on HCC angiogenesis and metastasis. HCC-derived exosomal miR-3174 was ingested by human umbilical vein endothelial cells (HUVECs) in which HIPK3 was targeted and silenced, causing subsequent inhibition of Fas and p53 signaling pathways. Furthermore, exosomal miR-3174 induced permeability and angiogenesis of HUVECs to enhance HCC progression and metastasis. Under hypoxia, upregulated HIF-1α further promoted the transcription of miR-3174. Moreover, HNRNPA1 augmented the package of miR-3174 into exosomes. Clinical data analysis confirmed that HCC patients with high-level miR-3174 were correlated with worse prognosis. Thus, exosomal miR-3174 induced by hypoxia promotes angiogenesis and metastasis of HCC by inhibiting HIPK3/p53 and HIPK3/Fas signaling pathways. Our findings might provide potential targets for anti-tumor therapy.

Keywords:  Cancer; Cell biology; Molecular biology

DOI:  https://doi.org/10.1016/j.isci.2024.108955
J Yeungnam Med Sci. 2024 Feb 08.

Clinical significance of exosomal noncoding RNAs in hepatocellular carcinoma: a narrative review.

Jae Sung Yoo, Min Kyu Kang.

  Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide, with poor prognosis owing to its high frequency of recurrence and metastasis. Moreover, most patients are diagnosed at an advanced stage owing to a lack of early detection markers. Exosomes, which are characterized by their cargos of stable intracellular messengers, such as DNA, RNA, proteins, and lipids, play a crucial role in regulating cell differentiation and HCC development. Recently, exosomal noncoding RNAs (ncRNAs), including microRNAs, long ncRNAs, and circular RNAs, have become increasingly important diagnostic, prognostic, and predictive markers of HCC. Herein, we discuss the clinical implications of exosomal ncRNAs, specifically those within the HCC regulatory network.

Keywords:  Circular RNA; Exosomes; Hepatocellular carcinoma; Long noncoding RNA; MicroRNAs

DOI:  https://doi.org/10.12701/jyms.2023.01186
Int Immunopharmacol. 2024 Feb 04. pii: S1567-5769(24)00108-5. [Epub ahead of print]129 111590

Macrophage-derived exosomal microRNAs promote metastasis in pancreatic ductal adenocarcinoma.

Yi Chen, Yangyang Lei, Jianke Li, Xiaolin Wang, Guoping Li.

   BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly invasive disease that can metastasize to distant organs such as the lung and liver. However, the exact mechanisms underlying PDAC metastasis remain unclear. Tumor-associated macrophages (TAMs) have been shown to play a critical role in cancer initiation, progression, outgrowth, and metastasis, likely through their interaction with cancer cells via extracellular vesicles known as exosomes. However, the precise mechanisms of this interaction are not fully understood.
METHODS: In this study, we obtained TAMs from PDAC patients and isolated exosomes from their culture medium. We characterized these exosomes and analyzed their miRNA expression profiles using Multiplex miRNA assays with FirePlex particle technology. Additionally, we conducted in vitro co-culture experiments between PDAC cells and conditioned media or exosomes from TAMs to investigate the crosstalk between these cells via exosomes. Furthermore, we evaluated the in vivo lung metastasis of PDAC cells treated with TAM-derived exosomes in athymic nude mice.
RESULTS: TAMs from PDAC patients promoted the invasiveness and migratory potential of PDAC cells, partially through the effects of TAM-derived exosomes. Specifically, we identified two microRNAs, miR-202-5p and miR-142-5p, which were transferred from TAM-derived exosomes to PDAC cells, resulting in the suppression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and promoting their invasiveness and migratory potential. We also found that distal metastasis was increased in PDAC cells treated with TAM-derived exosomes, partially through miR-202-5p and miR-142-5p.
CONCLUSIONS: Exosomal transfer of miR-202-5p and miR-142-5p plays a significant role in conferring invasiveness and migratory potential to PDAC cells. Targeting exosome communication may represent a promising new therapeutic strategy for reducing cancer metastasis of PDACs.

Keywords:  Cancer metastasis; Exosomes; Phosphatase and tensin homolog deleted on chromosome ten (PTEN); Tumor-associated macrophages (TAMs); miRNAs; pancreatic ductal adenocarcinoma (PDAC)

DOI:  https://doi.org/10.1016/j.intimp.2024.111590
Biomed Pharmacother. 2024 Feb 02. pii: S0753-3322(24)00116-1. [Epub ahead of print]172 116235

Unveiling the role of ferroptosis-associated exosomal non-coding RNAs in cancer pathogenesis.

Yiping Zhang, Jun Xie.

  The pivotal regulatory role of non-coding RNAs (ncRNAs), especially exosomal ncRNAs, in ferroptosis significantly influences cancer cell fate. This review explores their involvement across various human cancers, focusing on microRNAs (miRNA), long non-coding RNAs (lncRNA), and circular RNAs (circRNA). These ncRNAs either stimulate or inhibit ferroptosis by targeting key components, impacting cancer susceptibility to this form of cell death. Specific studies in lung, gastric, liver, cervical, bladder, pancreatic, and osteosarcoma cancers underscore the crucial role of exosomal ncRNAs in modulating ferroptosis, influencing cancer progression, and therapeutic responses. Emphasizing the therapeutic potential of exosomal ncRNAs, we discuss their ability to deliver circRNA, miRNA, and lncRNA to target cells. Despite being in early stages with challenges in bioengineering for drug delivery, these studies hold promise for future clinical applications. Noteworthy findings include inhibiting exosome production to overcome ferroptosis resistance in lung adenocarcinoma and the potential of exosomal DACT3-AS1 to sensitize gastric cancer cells to ferroptosis. The review concludes by highlighting exosomal ncRNAs like miR-4443 and miR-660-5p as promising therapeutic targets, offering avenues for precise cancer interventions by modulating signaling pathways and sensitizing cells to ferroptosis. Overall, this review enhances our understanding of cancer pathogenesis and presents new horizons for targeted therapeutic interventions, revealing the intricate interplay between exosomal ncRNAs and ferroptosis.

Keywords:  Cancer; Exosomes; Ferroptosis; Non-coding RNAs

DOI:  https://doi.org/10.1016/j.biopha.2024.116235
Sichuan Da Xue Xue Bao Yi Xue Ban. 2024 Jan 20. 55(1): 6-12

[Hepatocellular Carcinoma-Derived Exosomes: Key Players in Intercellular Communication Within the Tumor Microenvironment].

Tang Feng, Xinrui Yang, Qiwei Wang, Xiaoheng Liu.

  Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the world. Due to the insidious onset and rapid progression and a lack of effective treatments, the prognosis of patients with HCC is extremely poor, with the average 5-year survival rate being less than 10%. The tumor microenvironment (TME), the internal environment in which HCC develops, can regulate the oncogenesis, development, invasion, and metastasis of HCC. During the process of cancer progression, HCC cells can regulate the biological behaviors of tumor cells, cancer-associated fibroblasts, cancer-associated immune cells, and other cells in the TME by releasing exosomes containing specific signals, thereby promoting cancer progression. However, the exact molecular mechanisms and the roles of exosomes in the specific cellular regulation of these processes are not fully understood. Herein, we summarized the TME components of HCC, the sources and the biological traits of exosomes in the TME, and the impact of mechanical factors on exosomes. In addition, special attention was given to the discussion of the effects of HCC-exosomes on different types of cells in the microenvironment. There are still many difficulties to be overcome before exosomes can be applied as carriers in clinical cancer treatment. First of all, the homogeneity of exosomes is difficult to ensure. Secondly, exosomes are mainly administered through subcutaneous injection. Although this method is simple and easy to implement, the absorption efficiency is not ideal. Thirdly, exosome extraction methods are limited in number and inefficient, making it difficult to prepare exosomes in large quantities. It is important to ensure that exosomes are used in sufficient quantities to trigger an effective tumor immune response, especially for exosome-mediated tumor immunotherapy. With the improvement in identification, isolation, and purification technology, exosomes are expected to be successfully used in the clinical diagnosis of early-stage HCC and the clinical treatment of liver cancer.

Keywords:  Exosomes; Hepatocellular carcinoma; Intercellular communication; Review; Tumor microenvironment

DOI:  https://doi.org/10.12182/20240160203
Front Cell Dev Biol. 2024 ;12 1323348

The biological role of extracellular vesicles in gastric cancer metastasis.

Yun Lei, Shuang Cai, Chun-Dong Zhang, Yong-Shuang Li.

  Gastric cancer (GC) is a tumor characterized by high incidence and mortality, with metastasis being the primary cause of poor prognosis. Extracellular vesicles (EVs) are an important intercellular communication medium. They contain bioactive substances such as proteins, nucleic acids, and lipids. EVs play a crucial biological role in the process of GC metastasis. Through mechanisms such as remodeling the tumor microenvironment (TME), immune suppression, promoting angiogenesis, and facilitating epithelial-mesenchymal transition (EMT) and mesothelial-mesenchymal transition (MMT), EVs promote invasion and metastasis in GC. Further exploration of the biological roles of EVs will contribute to our understanding of the mechanisms underlying GC metastasis and may provide novel targets and strategies for the diagnosis and treatment of GC. In this review, we summarize the mechanisms by which EVs influence GC metastasis from four aspects: remodeling the TME, modulating the immune system, influencing angiogenesis, and modulating the processes of EMT and MMT. Finally, we briefly summarized the organotropism of GC metastasis as well as the potential and limitations of EVs in GC.

Keywords:  epithelial-mesenchymal transition; extracellular vesicles; gastric cancer; metastasis; tumor microenvironment

DOI:  https://doi.org/10.3389/fcell.2024.1323348
J Nanobiotechnology. 2024 Feb 08. 22(1): 55

Polydopamine-assisted aptamer-carrying tetrahedral DNA microelectrode sensor for ultrasensitive electrochemical detection of exosomes.

Bowen Jiang, Tenghua Zhang, Silan Liu, Yan Sheng, Jiaming Hu.

   BACKGROUND: Exosomes are nanoscale extracellular vesicles (30-160 nm) with endosome origin secreted by almost all types of cells, which are considered to be messengers of intercellular communication. Cancerous exosomes serve as a rich source of biomarkers for monitoring changes in cancer-related physiological status, because they carry a large number of biological macromolecules derived from parental tumors. The ultrasensitive quantification of trace amounts of cancerous exosomes is highly valuable for non-invasive early cancer diagnosis, yet it remains challenging. Herein, we developed an aptamer-carrying tetrahedral DNA (Apt-TDNA) microelectrode sensor, assisted by a polydopamine (PDA) coating with semiconducting properties, for the ultrasensitive electrochemical detection of cancer-derived exosomes.
RESULTS: The stable rigid structure and orientation of Apt-TDNA ensured efficient capture of suspended exosomes. Without PDA coating signal amplification strategy, the sensor has a linear working range of 102-107 particles mL-1, with LOD of ~ 69 exosomes and ~ 42 exosomes for EIS and DPV, respectively. With PDA coating, the electrochemical signal of the microelectrode is further amplified, achieving single particle level sensitivity (~ 14 exosomes by EIS and ~ 6 exosomes by DPV).
CONCLUSIONS: The proposed PDA-assisted Apt-TDNA microelectrode sensor, which integrates efficient exosome capture, sensitive electrochemical signal feedback with PDA coating signal amplification, provides a new avenue for the development of simple and sensitive electrochemical sensing techniques in non-invasive cancer diagnosis and monitoring treatment response.

Keywords:  Aptamer; Electrochemical sensing; Exosomes; Microelectrode; Polydopamine; Tetrahedra DNA

DOI:  https://doi.org/10.1186/s12951-024-02318-6
Int J Mol Sci. 2024 Jan 24. pii: 1407. [Epub ahead of print]25(3):

RNA Profile of Cell Bodies and Exosomes Released by Tumorigenic and Non-Tumorigenic Thyroid Cells.

Valentina Maggisano, Francesca Capriglione, Catia Mio, Stefania Bulotta, Giuseppe Damante, Diego Russo, Marilena Celano.

  Tumor cells release exosomes, extracellular vesicle containing various bioactive molecules such as protein, DNA and RNA. The analysis of RNA molecules packaged in exosomes may provide new potential diagnostic or prognostic tumor biomarkers. The treatment of radioiodine-refractory aggressive thyroid cancer is still an unresolved clinical challenge, and the search for biomarkers that are detectable in early phase of the disease has become a fundamental goal for thyroid cancer research. By using transcriptome analysis, this study aimed to analyze the gene expression profiles of exosomes secreted by a non-tumorigenic thyroid cell line (Nthy-ori 3.1-exo) and a papillary thyroid cancer (TPC-1-exo) cell line, comparing them with those of cell bodies (Nthy-ori 3.1-cells and TPC-1-cells). A total of 9107 transcripts were identified as differentially expressed when comparing TPC-1-exo with TPC-1-cells and 5861 when comparing Nthy-ori 3.1-exo with Nthy-ori 3.1-cells. Among them, Sialic acid-binding immunoglobulin-like lectins 10 and 11 (SIGLEC10, SIGLEC11) and Keratin-associated protein 5 (KRTAP5-3) transcripts, genes known to be involved in cancer progression, turned out to be up-regulated only in TPC-1-exo. Gene ontology analysis revealed significantly enriched pathways, and only in TPC-1-exo were the differential expressed genes associated with an up-regulation in epigenetic processes. These findings provide a proof of concept that some mRNA species are specifically packaged in tumor-cell-derived exosomes and may constitute a starting point for the identification of new biomarkers for thyroid tumors.

Keywords:  RNAs; exosomes; therapeutic strategies; thyroid cancer cells; transcriptome

DOI:  https://doi.org/10.3390/ijms25031407
Biomed Environ Sci. 2024 Jan 20. 37(1): 71-84

Exosome-Transmitted miR-224-5p Promotes Colorectal Cancer Cell Proliferation via Targeting ULK2 in p53-Dependent Manner.

Le Mei Yang, Qi Zheng, Xiao Jia Liu, Xian Xian Li, Lim Veronica, Qi Chen, Zhong Hua Zhao, Shu Yang Wang.

   Objective: To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer (CRC).
Methods: The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR, respectively. Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p. The protein expressions of p53 and unc-51 like kinase 2 (ULK2) in CRC cells were detected by western blot. Flow cytometry was used to detect cell cycle and apoptosis. Cell proliferation was measured by CCK8 and EdU assay.
Results: The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage. CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner, and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine. Moreover, ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues. Interestingly, ULK2 inhibited CRC cell proliferation in a p53-dependent manner. Furthermore, exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.
Conclusion: Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC, which may offer promising targets for CRC prevention and therapy.

Keywords:  Cell proliferation; Colorectal cancer; Exosome; ULK2; miR-224-5p; p53

DOI:  https://doi.org/10.3967/bes2023.144
Cancers (Basel). 2024 Jan 29. pii: 567. [Epub ahead of print]16(3):

Emerging Roles of Small Extracellular Vesicles in Gastrointestinal Cancer Research and Therapy.

Nora Schneider, Patrick Christian Hermann, Tim Eiseler, Thomas Seufferlein.

  Discovered in the late eighties, sEVs are small extracellular nanovesicles (30-150 nm diameter) that gained increasing attention due to their profound roles in cancer, immunology, and therapeutic approaches. They were initially described as cellular waste bins; however, in recent years, sEVs have become known as important mediators of intercellular communication. They are secreted from cells in substantial amounts and exert their influence on recipient cells by signaling through cell surface receptors or transferring cargos, such as proteins, RNAs, miRNAs, or lipids. A key role of sEVs in cancer is immune modulation, as well as pro-invasive signaling and formation of pre-metastatic niches. sEVs are ideal biomarker platforms, and can be engineered as drug carriers or anti-cancer vaccines. Thus, sEVs further provide novel avenues for cancer diagnosis and treatment. This review will focus on the role of sEVs in GI-oncology and delineate their functions in cancer progression, diagnosis, and therapeutic use.

Keywords:  biomarkers; gastrointestinal cancer; metastasis; pre-metastatic niches; sEVs; small extracellular vesicles; therapeutic sEVs

DOI:  https://doi.org/10.3390/cancers16030567
ACS Nano. 2024 Feb 09.

"Triple-Punch" Strategy Exosome-Mimetic Nanovesicles for Triple Negative Breast Cancer Therapy.

Chenhong Zhang, Shuangshuang Tang, Meilin Wang, Luhan Li, Jun Li, Dekun Wang, Xue Mi, Yuying Zhang, Xiaoyue Tan, Shijing Yue.

  Triple-negative breast cancer (TNBC) is the most malignant breast cancer, with high rates of relapse and metastasis. Because of the nonspecific targeting of chemotherapy and insurmountable aggressiveness, TNBC therapy lacks an effective strategy. Exosomes have been reported as an efficient drug delivery system (DDS). CD82 is a tumor metastasis inhibitory molecule that is enriched in exosomes. Aptamer AS1411 specifically targets TNBC cells due to its high expression of nucleolin. We generated a "triple-punch" cell membrane-derived exosome-mimetic nanovesicle system that integrated with CD82 overexpression, AS1411 conjugation, and doxorubicin (DOX) delivery. CD82 enrichment effectively inhibits the migration of TNBC cells. AS1411 conjugation specifically targets TNBC cells. DOX loading effectively inhibits proliferation and induces apoptosis of TNBC cells. Our results demonstrate a system of exosome-mimetic nanovesicles with "triple-punch" that may facilitate TNBC therapeutics.

Keywords:  Aptamer AS1411; CD82; Exosome; Nanovesicle; Triple-negative breast cancer

DOI:  https://doi.org/10.1021/acsnano.3c10568
Mol Neurobiol. 2024 Feb 07.

Exosomal circZNF800 Derived from Glioma Stem-like Cells Regulates Glioblastoma Tumorigenicity via the PIEZO1/Akt Axis.

Ning Zhang, Pengfei Wu, Maolin Mu, Chaoshi Niu, Shanshan Hu.

  Exosomes play a crucial role in regulating crosstalk between tumor and tumor stem-like cells through their cargo molecules. Circular RNAs (circRNAs) have recently been demonstrated to be critical factors in tumorigenesis. This study focuses on the molecular mechanism by which circRNAs from glioma stem-like cell (GSLC) exosomes regulate glioblastoma (GBM) tumorigenicity. In this study, we validated that GSLC exosomes accelerated the malignant phenotype of GBM. Subsequently, we found that circZNF800 was highly expressed in GSLC exosomes and was negatively associated with GBM patients. CircZNF800 promoted GBM cell proliferation and migration and inhibited GBM cell apoptosis in vitro. Silencing circZNF800 could improve the GBM xenograft model survival rate. Mechanistic studies revealed that circZNF800 activated the PIEZO1/Akt signaling pathway by sponging miR-139-5p. CircZNF800 derived from GSLC exosomes promoted GBM cell tumorigenicity and predicted poor prognosis in GBM patients. CircZNF800 has the potential to serve as a promising target for further therapeutic exploration.

Keywords:  Exosome; Glioma stem-like cell; PIEZO1; circZNF800; miR-139-5p

DOI:  https://doi.org/10.1007/s12035-024-04002-0
Cancer Drug Resist. 2024 ;7 1

Acquisition of drug resistance in endothelial cells by tumor-derived extracellular vesicles and cancer progression.

Masahiro Morimoto, Nako Maishi, Kyoko Hida.

  Angiogenesis by endothelial cells (ECs) is essential for tumor growth. Angiogenesis inhibitors are used in combination with anticancer drugs in many tumor types, but tumors eventually become resistant. Previously, the underlying mechanism for developing drug resistance was considered to be a change in the characteristics of tumor cells whereas ECs were thought to be genetically stable and do not contribute to drug resistance. However, tumor endothelial cells (TECs) have been shown to differ from normal endothelial cells (NECs) in that they exhibit chromosomal abnormalities, angiogenic potential, and drug resistance. Extracellular vesicles (EVs) secreted by tumor cells have recently attracted attention as a factor involved in the acquisition of such abnormalities. Various cells communicate with each other through EVs, and it has been reported that tumor-derived EVs act on other tumor cells or stromal cells to develop drug resistance. Drug-resistant tumor cells confer drug resistance to recipient cells by transporting mRNAs encoding ATP-binding cassette subfamily B member 1 (ABCB1) and ATP-binding cassette subfamily C member 1 (ABCC1) as well as miRNAs involved in signaling such as Akt, drug efflux transporters, and P-glycoprotein modulators via EVs. However, there are limited reports on the acquisition of drug resistance in ECs by tumor-derived EVs. Since drug resistance of ECs may induce tumor metastasis and support tumor cell proliferation, the mechanism underlying the development of resistance should be elucidated to find therapeutic application. This review provides insight into the acquisition of drug resistance in ECs via tumor EVs in the tumor microenvironment.

Keywords:  Tumor endothelial cell; drug resistance; extracellular vesicles; miRNA

DOI:  https://doi.org/10.20517/cdr.2023.121