bims-exocan 2024-05-26 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2024–05–26
twelve papers selected by
Muhammad Rizwan, COMSATS University

Red Blood Cell-Derived Exosomal Oncogenic MicroRNA Promote Cancer Development and Progression.
Suppression of gastric cancer cell proliferation by miR-494-3p inhibitor-loaded engineered exosomes.
Exosomal circPOLQ promotes macrophage M2 polarization via activating IL-10/STAT3 axis in a colorectal cancer model.
Research on the mechanism of exosomes from different sources influencing the progression of lung cancer.
Multi-targeted nanoarrays for early broad-spectrum detection of lung cancer based on blood biopsy of tumor exosomes.
Role of tumor-derived exosomes mediated immune cell reprograming in cancer.
Challenges and opportunities for cancer stem cell-targeted immunotherapies include immune checkpoint inhibitor, cancer stem cell-dendritic cell vaccine, chimeric antigen receptor immune cells, and modified exosomes.
Bioengineering extracellular vesicle cargo for optimal therapeutic efficiency.
Revisiting the advances and challenges in the clinical applications of extracellular vesicles in cancer.
Extracellular vesicles in non-small cell lung cancer stemness and clinical applications.
Extracellular Vesicles in Breast Cancer: From Intercellular Communication to Therapeutic Opportunities.
Extracellular vesicle biomarkers in circulation for colorectal cancer detection: a systematic review and meta-analysis.

medRxiv. 2024 May 10. pii: 2024.05.10.24307177. [Epub ahead of print]

Red Blood Cell-Derived Exosomal Oncogenic MicroRNA Promote Cancer Development and Progression.

Jin Li, Pushpa Dhilipkannah, Van K Holden, Ashutosh Sachdeva, Feng Jiang.

The role of red blood cells (RBCs) in tumorigenesis is poorly understood. We previously identified RBC-microRNAs with aberrations linked to lung cancer, including miR-93-5p. Here we find that miR-93-5p levels are elevated in RBC-derived exosomes among lung cancer patients and are associated with their shorter survivals. RBC-derived miR-93-5p transfers to cancer cells primarily through the exosomal pathway. The transferred RBC-miR-93-5p can target PTEN in cancer cells, and hence increase cell proliferation, invasion, and migration. RBC-derived miR-93-5p accelerates, whereas targeting miR-93-5p diminishes tumor growth in xenograft models. These findings reveal a novel biological function of RBCs in tumorigenesis, where they facilitate cancer progression by transferring the oncomiR via exosomes, thereby offering new diagnostic and treatment strategies for lung cancer.

DOI: https://doi.org/10.1101/2024.05.10.24307177
Heliyon. 2024 May 30. 10(10): e30803

Suppression of gastric cancer cell proliferation by miR-494-3p inhibitor-loaded engineered exosomes.

Limin Zhang, Yingwei Xue, Hongfeng Zhang.

   Background: Gastric cancer necessitates novel treatments, and exosomes are promising therapeutic carriers. We created miR-494-3p inhibitor exosomes to assess their effects on gastric cancer cells.
Methods: We conducted a comprehensive investigation into the expression of the oncogenic miR-494-3p in gastric cancer tissues from patients. Subsequently, we engineered miR-494-3p inhibitor-loaded exosomes and characterized their morphology and size through transmission electron microscopy and nanoparticle tracking analysis. We next determined the encapsulation efficiency of the miR-494-3p inhibitor within these exosomes and evaluated the exosomes' structural integrity by quantifying the presence of exosomal markers. Following these validations, we co-cultured miR-494-3p inhibitor exosomes with cancer cells and employed PKH26 staining to visualize the efficient endocytosis of engineered exosomes by gastric cancer cells and assess the impact of these modified exosomes on gastric cancer cell proliferation, apoptosis, migration, and invasion.
Results: Increased expression of miR-494-3p was observed in gastric cancer tissues as compared to controls. Significant low miR-494-3p levels were found within miR-494-3p inhibitor exosomes, signifying effective encapsulation. The incorporation of miR-494-3p inhibitor into engineered exosomes did not alter exosome morphology or size. Finally, PKH26-stained exosomes clearly demonstrated efficient endocytosis by gastric cancer cells, leading to reduced proliferation, migration, invasion, and increased apoptosis.
Conclusion: Our study identifies elevated miR-494-3p in gastric cancer tissues prompting the development of miR-494-3p inhibitor-loaded exosomes with efficient encapsulation. These engineered exosomes demonstrate successful endocytosis by cancer cells. This highlights their potential for therapeutic use in gastric cancer treatment by suppressing proliferation, migration, and invasion while enhancing apoptosis.

Keywords:  Apoptosis; Exosome; Gastric cancer; miR-494-3p

DOI:  https://doi.org/10.1016/j.heliyon.2024.e30803
J Immunother Cancer. 2024 May 23. pii: e008491. [Epub ahead of print]12(5):

Exosomal circPOLQ promotes macrophage M2 polarization via activating IL-10/STAT3 axis in a colorectal cancer model.

Zhenqiang Sun, Yanxin Xu, Bo Shao, Pengyuan Dang, Shengyun Hu, Haifeng Sun, Chen Chen, Chaoguan Wang, Jinbo Liu, Yang Liu, Junhong Hu.

   BACKGROUND: Accumulating evidence demonstrates that an increased tumor-associated macrophage abundance is often associated with poor prognosis in colorectal cancer (CRC). The mechanism underlying the effect of tumor-derived exosomes on M2 macrophage polarization remains elusive.
RESULTS: The novel circular RNA circPOLQ exhibited significantly higher expression in CRC tissues than in paired normal tissues. Higher circPOLQ expression was associated with poorer prognosis in patients with CRC. In vitro and in vivo experiments showed that tumor-derived exosomal circPOLQ did not directly regulate CRC cell development but promoted CRC metastatic nodule formation by enhancing M2 macrophage polarization. circPOLQ activated the interleukin-10/signal transducer and activator of transcription 3 axis by targeting miR-379-3 p to promote M2 macrophage polarization.
CONCLUSION: circPOLQ can enter macrophages via CRC cell-derived exosomes and promote CRC metastatic nodule formation by enhancing M2 macrophage polarization. These findings reveal a tumor-derived exosome-mediated tumor-macrophage interaction potentially affecting CRC metastatic nodule formation.

Keywords:  colorectal cancer; immunity; macrophages; tumor microenvironment

DOI:  https://doi.org/10.1136/jitc-2023-008491
Environ Toxicol. 2024 May 18.

Research on the mechanism of exosomes from different sources influencing the progression of lung cancer.

Guangxian Mao, Jixian Liu.

  As a key regulator of intercellular communication, exosomes are essential for tumor cells. In our study, we will explore the mechanisms of exosomes from different sources on lung cancer. We isolated CD8+T cells and cancer-associated fibroblasts (CAFs) from venous blood and tumor tissues of lung cancer patients, and isolated exosomes. MiR-2682 was high expression in CD8+T-derived exosomes, and lncRNA-FOXD3-AS1 was upregulated in CAF-derived exosomes. Online bioinformatics database analysis showed that RNA Binding Motif Protein 39 (RBM39) was identified as the target of miR-2682, and eukaryotic translation initiation factors 3B (EIF3B) was identified as the RNA binding protein of FOXD3-AS1. CD8+T-derived exosomes inhibited the growth of A549 cells and promoted apoptosis, while miR-2682 inhibits reversed these effects of CD8+T-derived exosomes. CAF-derived exosomes promoted the growth of A549 cells and inhibited apoptosis, while FOXD3-AS1 siRNA reversed the effect of CAF-derived exosomes. Mechanism studies have found that miR-2682 inhibits the growth of lung cancer cells by inhibiting the expression of RBM39. FOXD3-AS1 promoted the growth of lung cancer cells by binding to EIF3B. In vivo experiments showed that CD8+T cell-derived exosome miR-2682 inhibited lung cancer tumor formation, while CAF-derived exosome FOXD3-AS1 promoted lung cancer tumor formation. This study provides mechanistic insights into the role of miR-2682 and FOXD3-AS1 in lung cancer progression and provides new strategies for lung cancer treatment.

Keywords:  CD8+T cells; exosomes; lncRNA‐FOXD3‐AS1; lung cancer; miR‐2682; tumor‐associated fibroblasts

DOI:  https://doi.org/10.1002/tox.24292
Talanta. 2024 May 16. pii: S0039-9140(24)00649-0. [Epub ahead of print]276 126270

Multi-targeted nanoarrays for early broad-spectrum detection of lung cancer based on blood biopsy of tumor exosomes.

Shu Lian, Qixuan Wang, Yuxin Liu, Yusheng Lu, Lu Huang, Haohua Deng, Xiaodong Xie.

  Liquid biopsies utilizing tumor exosomes offer a noninvasive approach for cancer diagnosis. However, validation studies consistently report that in the early stages of cancer, the secretion of exosomes by cancer cells is relatively low, while bodily fluids exhibit a high abundance of other interfering biomolecules. Additionally, target mutations or differences in biomarker expression among various lung cancer subtypes may contribute to detection failures. In this study, we propose a targeted nanoarray-based early cancer diagnostic approach for multiple subtypes of lung cancer. The targeted nanoarray was constructed by modifying five targeting aptamers onto mesoporous silica nanoparticles through the conjugation between amino and carboxyl groups. The flow cytometry experiments demonstrated the specific recognition ability of the targeted nanoarray to tumor exosomes in PBS, even at biomarker expression levels as low as 1.5 %. Moreover, the TEM results indicated that the targeted nanoarray could isolate tumor exosomes in the blood of tumor-bearing mice. Furthermore, the targeted nanoarray could detect tumor exosomes in the blood of various lung cancer bearing mice, including at the early stages of cancer, which has just been established for 7 days. Overall, the targeted nanoarray represents a promising tool for the early detection of various subtypes of lung cancer.

Keywords:  Cancer early diagnosis; Liquid biopsy; Multi-subtypes lung cancer; Targeted nanoarray; Tumor exosomes

DOI:  https://doi.org/10.1016/j.talanta.2024.126270
Gene. 2024 May 22. pii: S0378-1119(24)00482-7. [Epub ahead of print] 148601

Role of tumor-derived exosomes mediated immune cell reprograming in cancer.

Zening Liu, Zichao Chen, Jing Zhang, Junqiu Liu, Baohong Li, Zhenyong Zhang, Meichao Cai, Zhen Zhang.

  Tumor-derived exosomes (TDEs), as topologies of tumor cells, not only carry biological information from the mother, but also act as messengers for cellular communication. It has been demonstrated that TDEs play a key role in inducing an immunosuppressive tumor microenvironment (TME). They can reprogram immune cells indirectly or directly by delivering inhibitory proteins, cytokines, RNA and other substances. They not only inhibit the maturation and function of dendritic cells (DCs) and natural killer (NK) cells, but also remodel M2 macrophages and inhibit T cell infiltration to promote immunosuppression and create a favorable ecological niche for tumor growth, invasion and metastasis. Based on the specificity of TDEs, targeting TDEs has become a new strategy to monitor tumor progression and enhance treatment efficacy. This paper reviews the intricate molecular mechanisms underlying the immunosuppressive effects induced by TDEs to establish a theoretical foundation for cancer therapy. Additionally, the challenges of TDEs as a novel approach to tumor treatment are discussed.

Keywords:  Dendritic cells; Immunosuppressive; Macrophage; Natural killer cells; T cells; Tumor-derived exosomes

DOI:  https://doi.org/10.1016/j.gene.2024.148601
J Biochem Mol Toxicol. 2024 Jun;38(6): e23719

Challenges and opportunities for cancer stem cell-targeted immunotherapies include immune checkpoint inhibitor, cancer stem cell-dendritic cell vaccine, chimeric antigen receptor immune cells, and modified exosomes.

Abdullah Alqarni, Saade Abdalkareem Jasim, Farag M A Altalbawy, Harpreet Kaur, Irwanjot Kaur, Carlos Rodriguez-Benites, Mahamedha Deorari, Enas R Alwaily, Ahmed M Al-Ani, Ahmed H Redhee.

  Cancer stem cells (CSCs) are associated with the tumor microenvironment (TME). CSCs induce tumorigenesis, tumor recurrence and progression, and resistance to standard therapies. Indeed, CSCs pose an increasing challenge to current cancer therapy due to their stemness or self-renewal properties. The molecular and cellular interactions between heterogeneous CSCs and surrounding TME components and tumor-supporting immune cells show synergistic effects toward treatment failure. In the immunosuppressive TME, CSCs express various immunoregulatory proteins, growth factors, metabolites and cytokines, and also produce exosomes, a type of extracellular vesicles, to protect themselves from host immune surveillance. Among these, the identification and application of CSC-derived exosomes could be considered for the development of therapeutic approaches to eliminate CSCs or cancer, in addition to targeting the modulators that remodel the composition of the TME, as reviewed in this study. Here, we introduce the role of CSCs and how their interaction with TME complicates immunotherapies, and then present the CSC-based immunotherapy and the limitation of these therapies. We describe the biology and role of tumor/CSC-derived exosomes that induce immune suppression in the TME, and finally, introduce their potentials for the development of CSC-based targeted immunotherapy in the future.

Keywords:  cancer stem cell; cancer vaccine; chimeric antigen receptor T cell; exosomes; immune escape; immunotherapy

DOI:  https://doi.org/10.1002/jbt.23719
Mol Ther Methods Clin Dev. 2024 Jun 13. 32(2): 101259

Bioengineering extracellular vesicle cargo for optimal therapeutic efficiency.

Charlotte A René, Robin J Parks.

  Extracellular vesicles (EVs) have the innate ability to carry proteins, lipids, and nucleic acids between cells, and thus these vesicles have gained much attention as potential therapeutic delivery vehicles. Many strategies have been explored to enhance the loading of specific cargoes of interest into EVs, which could result in the delivery of more therapeutic to recipient cells, thus enhancing therapeutic efficacy. In this review, we discuss the natural biogenesis of EVs, the mechanism by which proteins and nucleic acids are selected for inclusion in EVs, and novel methods that have been employed to enhance loading of specific cargoes into EVs. As well, we discuss biodistribution of administered EVs in vivo and summarize clinical trials that have attempted to harness the therapeutic potential of EVs.

Keywords:  biodistribution; bioengineering; exosomes; extracellular vesicles; therapeutic delivery

DOI:  https://doi.org/10.1016/j.omtm.2024.101259
Cancer Lett. 2024 May 16. pii: S0304-3835(24)00353-7. [Epub ahead of print] 216960

Revisiting the advances and challenges in the clinical applications of extracellular vesicles in cancer.

Guangpeng He, Jiaxing Liu, Yifan Yu, Shibo Wei, Xueqiang Peng, Liang Yang, Hangyu Li.

  Extracellular vesicles (EVs) have been the subject of an exponentially growing number of studies covering their biogenesis mechanisms, isolation and analysis techniques, physiological and pathological roles, and clinical applications, such as biomarker and therapeutic uses. Nevertheless, the heterogeneity of EVs both challenges our understanding of them and presents new opportunities for their potential application. Recently, the EV field experienced a wide range of advances. However, the challenges also remain huge. This review focuses on the recent progress and difficulties encountered in the practical use of EVs in clinical settings. In addition, we also explored the concept of EV heterogeneity to acquire a more thorough understanding of EVs and their involvement in cancer, specifically focusing on the fundamental nature of EVs.

Keywords:  EV heterogeneity; biomarker; drug delivery; tumor microenvironment

DOI:  https://doi.org/10.1016/j.canlet.2024.216960
Front Immunol. 2024 ;15 1369356

Extracellular vesicles in non-small cell lung cancer stemness and clinical applications.

Prita Pandya, Dania S Al-Qasrawi, Skyeler Klinge, Verline Justilien.

  Non-small cell lung carcinoma (NSCLC) accounts for 85% of lung cancers, the leading cause of cancer associated deaths in the US and worldwide. Within NSCLC tumors, there is a subpopulation of cancer cells termed cancer stem cells (CSCs) which exhibit stem-like properties that drive NSCLC progression, metastasis, relapse, and therapeutic resistance. Extracellular vesicles (EVs) are membrane-bound nanoparticles secreted by cells that carry vital messages for short- and long-range intercellular communication. Numerous studies have implicated NSCLC CSC-derived EVs in the factors associated with NSCLC lethality. In this review, we have discussed mechanisms of EV-directed cross-talk between CSCs and cells of the tumor microenvironment that promote stemness, tumor progression and metastasis in NSCLC. The mechanistic studies discussed herein have provided insights for developing novel NSCLC diagnostic and prognostic biomarkers and strategies to therapeutically target the NSCLC CSC niche.

Keywords:  biomarkers; cancer stem cells; extracellular vesicles; metastasis; non-small cell lung cancer; oncogenic signaling; therapeutic targeting; tumor microenvironment

DOI:  https://doi.org/10.3389/fimmu.2024.1369356
Pharmaceutics. 2024 May 14. pii: 654. [Epub ahead of print]16(5):

Extracellular Vesicles in Breast Cancer: From Intercellular Communication to Therapeutic Opportunities.

Barathan Muttiah, Sook Luan Ng, Yogeswaran Lokanathan, Min Hwei Ng, Jia Xian Law.

  Breast cancer, a multifaceted and heterogeneous disease, poses significant challenges in terms of understanding its intricate resistance mechanisms and devising effective therapeutic strategies. This review provides a comprehensive overview of the intricate landscape of extracellular vesicles (EVs) in the context of breast cancer, highlighting their diverse subtypes, biogenesis, and roles in intercellular communication within the tumour microenvironment (TME). The discussion spans various aspects, from EVs and stromal cells in breast cancer to their influence on angiogenesis, immune response, and chemoresistance. The impact of EV production in different culture systems, including two dimensional (2D), three dimensional (3D), and organoid models, is explored. Furthermore, this review delves into the therapeutic potential of EVs in breast cancer, presenting emerging strategies such as engineered EVs for gene delivery, nanoplatforms for targeted chemotherapy, and disrupting tumour derived EVs as a treatment approach. Understanding these complex interactions of EV within the breast cancer milieu is crucial for identifying resistance mechanisms and developing new therapeutic targets.

Keywords:  breast cancer; drug delivery; extracellular vesicles; nanotechnology; therapeutic resistance

DOI:  https://doi.org/10.3390/pharmaceutics16050654
BMC Cancer. 2024 May 22. 24(1): 623

Extracellular vesicle biomarkers in circulation for colorectal cancer detection: a systematic review and meta-analysis.

Xianquan Shi, Xinyu Zhao, Jinru Xue, Erna Jia.

  We provided an overview which evaluated the diagnostic performance of circulation EV biomarkers for CRC from PubMed, Medline, and Web of Science until 21 August 2022.Weidentified 48 studies that involved 7727 participants and evaluated 162 plasma/serum individual EV biomarkers including 117 RNAs and 45 proteins, as well as 45 EV biomarker panels for CRC detection. 12 studies evaluated the diagnostic performance of EV biomarkers for early CRC. The summarized sensitivity, specificity, and AUC value of individual EV RNAs and EV RNA panels were 76%, 75%, 0.87 and 82%, 79% and 0.90, respectively. Meanwhile, those of individual EV proteins and EV protein panels were 85%, 84%, 0.92 and 87%, 83%, 0.92, respectively. These results indicated that EV biomarker panels revealed superior diagnostic performance than the corresponding individual biomarkers. In early CRC, EV biomarkers showed available diagnostic value with the sensitivity, specificity, and AUC value of 80%, 75%, and 0.89.In subgroup analyses, EV miRNAs and LncRNAs held similar diagnostic value with the sensitivity, specificity and AUC value of 75%, 78%, 0.90 and 79%, 72%, 0.83, which was highly consistent with the whole EV RNAs. Significantly, the diagnostic values of EV miRNAs in plasma were marginally higher than those based on serum. In detail, the sensitivity, specificity, and AUC values were 79%, 81%, and 0.92 in plasma, as well as 74%, 77%, and 0.88 in serum, respectively. Therefore, circulation EV biomarkers could be considered as a promising biomarker for the early detection of CRC.

Keywords:  Biomarker; Circulation; Colorectal cancer; Diagnosis; Extracellular vesicles

DOI:  https://doi.org/10.1186/s12885-024-12312-8