bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2024–03–03
eleven papers selected by
Muhammad Rizwan, COMSATS University



  1. Assay Drug Dev Technol. 2024 Feb 26.
      Cancer is one of the leading causes of mortality worldwide. As the population increases, there is an enriched thrust for screening a newer delivery system for anticancer agents to treat cancer. Therefore, exosome-mediated cell communication is the hallmark of its participation in cancer metastasis and progression. Furthermore, the inward budding of endosomes is referred to as the multivesicular body. Exosome constitutes phospholipid bilayer-bound vesicles. It transfers bioactive compounds between various cells and the tumor microenvironment. In addition, they were selectively loading oncogenic molecules into exosomes for drug delivery. Exosome act as a potential biomarker in detecting therapeutic targets. Furthermore, exosomes fused with the cell membrane and were used as a diagnostic tool for cancer therapy. Exosomes are used in several ways to inhibit cancer cell growth. It can also carry genetic information and anticancer medications, preventing tumor cells from releasing exosomes. In addition, exosome-based drug delivery is utilized for preclinical and clinical trials, promoting the development of newer anticancer agents that suppress cancer growth. Exosomes further improve the immune system and help to generate new blood vessels. It blocks apoptosis and prevents cancer resistance. Exosomes act as cargo, allowing them to load proteins, chemotherapeutics, RNAs, DNAs, and hydrophobic drugs. Exosomes help to achieve advancement in cancer management through the use of precision medicine. The current review highlighted significant aspects of exosomes for cancer mechanism and prevention. Furthermore, novel strategies aimed to promote the clinical application of exosomes in cancer diagnosis and therapeutic impact. Finally, this review plays a pivotal role for the researchers in the industry and academics working in this field.
    Keywords:  bioactive compound; biomarker; cancer; exosomes; metastasis; multivesicular vesicles
    DOI:  https://doi.org/10.1089/adt.2023.026
  2. Cell Biochem Funct. 2024 Mar;42(2): e3960
      Exosomes have a significant impact on tumor survival, proliferation, metastasis, and recurrence. They also open up new therapeutic options and aid in the pathological identification and diagnosis of cancers. Exosomes have been shown in numerous studies to be essential for facilitating cell-to-cell communication. In B-cell hematological malignancies, the proteins and RNAs that are encased by circulating exosomes are thought to represent prospective sources for therapeutic drugs as well as biomarkers for diagnosis and prognosis. Additionally, exosomes can offer a "snapshot" of the tumor and the metastatic environment at any given point in time. In this review study, we concluded that leukemia-derived exosomes could be utilized as prognostic, diagnostic, and therapeutic biomarkers for individuals suffering from leukemia. Moreover, clinical studies have demonstrated that immune cells like dendritic cells create exosomes, which have the ability to activate the immune system against leukemia.
    Keywords:  exosomes; extracellular vesicles; immunotherapy; leukemia; pathobiology
    DOI:  https://doi.org/10.1002/cbf.3960
  3. Clin Chim Acta. 2024 Feb 28. pii: S0009-8981(24)00090-1. [Epub ahead of print]556 117849
      Colorectal cancer (CRC) is a type of gastrointestinal cancer with high morbidity and mortality rates, and is often accompanied by distant metastases. Metastasis is a major cause of shortened survival time and poor treatment outcomes for patients with CRC. However, the molecular mechanisms underlying the metastasis of CRC remain unclear. Exosomes are a class of small extracellular vesicles that originate from almost all human cells and can transmit biological information (e.g., nucleic acids, lipids, proteins, and metabolites) from secretory cells to target recipient cells. Recent studies have revealed that non-coding RNAs (ncRNAs) can be released by exosomes into the tumour microenvironment or specific tissues, and play a pivotal role in tumorigenesis by regulating a series of key molecules or signalling pathways, particularly those involved in tumour metastasis. Exosomal ncRNAs have potential as novel therapeutic targets for CRC metastasis, and can also be used as liquid biopsy biomarkers because of their specificity and sensitivity. Therefore, further investigations into the biological function and clinical value of exosomal ncRNAs will be of great value for the prevention, early diagnosis, and treatment of CRC metastasis.
    Keywords:  Biomarkers; Exosomes; Liquid biopsy; Therapy; Tumor metastasis; non-coding RNA
    DOI:  https://doi.org/10.1016/j.cca.2024.117849
  4. Front Cell Dev Biol. 2024 ;12 1344705
      Exosomes, extracellular vesicles secreted by cells, have garnered significant attention in recent years for their remarkable therapeutic potential. These nanoscale carriers can be harnessed for the targeted delivery of therapeutic agents, such as pharmaceuticals, proteins, and nucleic acids, across biological barriers. This versatile attribute of exosomes is a promising modality for precision medicine applications, notably in the realm of cancer therapy. However, despite their substantial therapeutic potential, exosomes still confront challenges tied to standardization and scalability that impede their practice in clinical applications. Moreover, heterogeneity in isolation methodologies and limited cargo loading mechanisms pose obstacles to ensuring consistent outcomes, thereby constraining their therapeutic utility. In contrast, exosomes exhibit a distinct advantage in cancer diagnosis, as they harbor specific signatures reflective of the tumor's genetic and proteomic profile. This characteristic endows them with the potential to serve as valuable liquid biopsies for non-invasive and real-time monitoring, making possible early cancer detection for the development of personalized treatment strategies. In this review, we provide an extensive evaluation of the advancements in exosome research, critically examining their advantages and limitations in the context of cancer therapy and early diagnosis. Furthermore, we present a curated overview of the most recent technological innovations utilizing exosomes, with a focus on enhancing the efficacy of early cancer detection.
    Keywords:  cancer; diagnosis; exosome; therapy; translational research
    DOI:  https://doi.org/10.3389/fcell.2024.1344705
  5. Cancer Lett. 2024 Feb 26. pii: S0304-3835(24)00152-6. [Epub ahead of print] 216759
      Exosomal circRNAs have emerged as promising biomarkers and therapeutic targets for urinary tumors. In this review, we explored the intricate role of exosomal circRNAs in urological cancers, focusing on their biological functions, dysregulation in tumors, and potential clinical applications. The review delves into the mechanisms by which exosomal circRNAs contribute to tumor progression and highlights their diagnostic and therapeutic implications. By synthesizing current research findings, we present a compelling case for the significance of exosomal circRNAs in the context of urinary tumors. Furthermore, the review discusses the challenges and opportunities associated with utilizing exosomal circRNAs as diagnostic tools and targeted therapeutic agents. There is a need for further research to elucidate the specific mechanisms of exosomal circRNA secretion and delivery, as well as to enhance the detection methods for clinical translational applications. Overall, this comprehensive review underscores the pivotal role of exosomal circRNAs in urinary tumors and underscores their potential as valuable biomarkers and therapeutic tools in the management of urological cancers.
    Keywords:  Biomarker; Circular RNA (circRNA); Exosome; Malignant progression; Urinary tumors
    DOI:  https://doi.org/10.1016/j.canlet.2024.216759
  6. J Exp Clin Cancer Res. 2024 Feb 27. 43(1): 59
       BACKGROUND: Hematological metastasis has been recognized as a crucial factor contributing to the high rates of metastasis and mortality observed in colorectal cancer (CRC). Notably, exosomes derived from cancer cells participate in the formation of CRC pre-metastatic niches; however, the mechanisms underlying their effects are largely unknown. While our preliminary research revealed the role of exosome-derived disintegrin and metalloproteinase 17 (ADAM17) in the early stages of CRC metastasis, the role of exosomal ADAM17 in CRC hematogenous metastasis remains unclear.
    METHODS: In the present study, we isolated and purified exosomes using ultracentrifugation and identified exosomal proteins through quantitative mass spectrometry. In vitro, co-culture assays were conducted to evaluate the impact of exosomal ADAM17 on the permeability of the blood vessel endothelium. Vascular endothelial cell resistance, the cell index, membrane protein separation, flow cytometry, and immunofluorescence were employed to investigate the mechanisms underlying exosomal ADAM17-induced vascular permeability. Additionally, a mouse model was established to elucidate the role of exosomal ADAM17 in the modulation of blood vessel permeability and pre-metastatic niche formation in vivo.
    RESULTS: Our clinical data indicated that ADAM17 derived from the circulating exosomes of patients with CRC could serve as a blood-based biomarker for predicting metastasis. The CRC-derived exosomal ADAM17 targeted vascular endothelial cells, thus enhancing vascular permeability by influencing vascular endothelial cadherin cell membrane localization. Moreover, exosomal ADAM17 mediated the formation of a pre-metastatic niche in nude mice by inducing vascular leakage, thereby promoting CRC metastasis. Nonetheless, ADAM17 selective inhibitors effectively reduced CRC metastasis in vivo.
    CONCLUSIONS: Our results suggest that exosomal ADAM17 plays a pivotal role in the hematogenous metastasis of CRC. Thus, this protein may serve as a valuable blood-based biomarker and potential drug target for CRC metastasis intervention.
    Keywords:  ADAM17; Colorectal cancer; Exosome; Hematogenous metastasis; VE-cadherin
    DOI:  https://doi.org/10.1186/s13046-024-02991-3
  7. Methods Mol Biol. 2024 Feb 28.
      Exosomes are small membrane-derived vesicles that transmit DNA constituents, mRNAs, microRNAs, and proteins from donor cells to a receiver cell. Various cells comprising of mesenchymal, immune, and cancer cells discharge exosomes. Cancer cell exosomes form the entry and reprogramming of essentials connected to a tumor environment. Melanoma-derived exosomes transport diverse proteins such as c-MET and RAB27a, which leave a melanoma mark. Increased mesenchymal epithelial transition (MET) expressions in serum exosomes have been considered an indicator of disease progression. Meanwhile, RAB27a has been identified as being involved in exosome discharge and trafficking. Decreased expressions of RAB27a in human melanoma cells have shown to diminish exosome release.We examined the effects of the downregulation and upregulation of RAB27a and c-MET in human dermal fibroblasts by utilizing the isolated exosomes of malignant melanoma cell lines. Melanoma exosomes derived from cancer cells conveyed information to healthy dermal fibroblasts and stem cells while inducing phenotypic change. In this chapter, we show optimized protocols that were used by our group for in vitro analysis with melanoma exosomes.
    Keywords:  Exosome isolation; Exosomes; Melanoma exosomes; RAB27a; c-MET
    DOI:  https://doi.org/10.1007/7651_2024_519
  8. Cell Commun Signal. 2024 Mar 01. 22(1): 156
      Exosomes are nanoscale extracellular vesicles present in bodily fluids that mediate intercellular communication by transferring bioactive molecules, thereby regulating a range of physiological and pathological processes. Exosomes can be secreted from nearly all cell types, and the biological function of exosomes is heterogeneous and depends on the donor cell type and state. Recent research has revealed that the levels of exosomes released from the endosomal system increase in cells undergoing programmed cell death. These exosomes play crucial roles in diseases, such as inflammation, tumors, and autoimmune diseases. However, there is currently a lack of systematic research on the differences in the biogenesis, secretion mechanisms, and composition of exosomes under different programmed cell death modalities. This review underscores the potential of exosomes as vital mediators of programmed cell death processes, highlighting the interconnection between exosome biosynthesis and the regulatory mechanisms governing cell death processes. Furthermore, we accentuate the prospect of leveraging exosomes for the development of innovative biomarkers and therapeutic strategies across various diseases.
    Keywords:  Biogenesis; Exosome; Programmed cell death; Regulatory mechanisms
    DOI:  https://doi.org/10.1186/s12964-024-01521-0
  9. Proteome Sci. 2024 Feb 28. 22(1): 4
       OBJECTIVE: Numerous evidence has highlighted the differences between primary tumors and metastases. Nonetheless, the differences in exosomal proteins derived from primary tumor and metastases remain elusive. Here, we aimed to identify differentially expressed exosomal proteins from primary canine mammary gland tumor and metastases to understand how they shape their own tumor microenvironment.
    METHODS: We clearly distinguished primary canine mammary gland tumors (CHMp) from metastases (CHMm) and profiled the proteins within their secreted exosomes using LC-MS/MS. Moreover, the abundance of glycolysis enzymes (GPI, LDHA) in CHMp exosome was verified with Western blotting, To broaden the scope, we extended to human colorectal cancer-derived exosomes (SW480 vs. SW620) for comparison.
    RESULTS: We identified significant differences in 87 and 65 proteins derived from CHMp and CHMm, respectively. Notably, glycolysis enzymes (GPI, LDHA, LDHB, TPI1, and ALDOA) showed specific enrichment in exosomes from the primary tumor.
    CONCLUSION: We observed significant differences in the cellular proteome between primary tumors and metastases, and intriguingly, we identified a parallel heterogeneity the protein composition of exosomes. Specifically, we reported that glycolysis enzymes were significantly enriched in CHMp exosomes compared to CHMm exosomes. We further demonstrated that this quantitative difference in glycolysis enzymes persisted across primary and metastases, extending to human colorectal cancer-derived exosomes (SW480 vs. SW620). Our findings of the specific enrichment of glycolysis enzymes in primary tumor-derived exosomes contribute to a better understanding of tumor microenvironment modulation and heterogeneity between primary tumors and metastases.
    Keywords:  Cancer; Exosome; Metastases; Primary tumor; Proteomics
    DOI:  https://doi.org/10.1186/s12953-023-00226-5
  10. Endocr Metab Immune Disord Drug Targets. 2024 Feb 28.
       BACKGROUND: The most aggressive form of breast cancer (BC) is Triple-Negative BC (TNBC), with the poorest prognosis, accounting for nearly 15% of all cases. Since there is no effective treatment, novel strategies, especially targeted therapies, are essential to treat TNBC. Exosomes are nano-sized microvesicles derived from cells and transport various intracellular cargoes, including microRNAs (miRNAs). MiRNAs, small non-coding RNA, are an influential factor in the development of cancerous transformations in cells.
    METHOD: Bioinformatics analysis of genes related to TNBC revealed that PTEN plays a crucial role in the disease. Relative expression of this gene was analyzed with RT-qPCR in 14 TNBC clinical samples. Electroporation was used to load miRNA antagomir into exosomes extracted from the conditioned medium. Then, the expression of miR-155 and PTEN was evaluated in MDA-MB-231 cells treated with antagomir-loaded exosomes.
    RESULTS: Based on the bioinformatics analysis, miR-155 is a potent inhibitor of PTEN. Following treatment with antagomir-loaded exosomes, RT-qPCR showed significantly reduced miR- 155 and increased PTEN levels in MDA-MB-231 cells.
    CONCLUSION: Based on the results of this study, exosomes can be effectively used as a cargo of oligonucleotides like miRNA mimics and antagomirs in targeted therapies.
    Keywords:  Breast Cancer; Exosome; PTEN; Triple-negative breast cancer; miR-155; therapies.
    DOI:  https://doi.org/10.2174/0118715303289859240214103350
  11. Biotechnol J. 2024 Feb;19(2): e2300296
      Doxorubicin (DOX) could be utilized to treat lung adenocarcinoma (LUAD), while dose-limiting cardiotoxicity limits its clinical utilization. MDA-MB-231 cell-derived exosomes show lung-specific organotropism features. In this study, we aimed to explore the potential of MDA-MB-231 cell-derived exosomes in DOX specific delivery to the lung. MDA-MB-231 cell-derived exosomes were coincubated with to construct for the doxorubicin delivery system (D-EXO). Exosomes labeled with fluorescein isothiocyanate were incubated with A549 cells or 293T cells, and the engulf and the mean intensity of the fluorescence were detected with immunofluorescence and flow cytometry assay. Cell viability was detected with cell counting kit-8 (CCK-8), and cell migration was determined by scratch test. The protein expression was detected by Western blot assay. A549 cell line-derived xenograft mouse model was constructed to examine the treatment effect of D-EXO. MDA-MB-231 cell-derived exosomes could be specially taken up by A549 cells with diminished cell viability but not engulfed by 293T cells. D-EXO inhibited A549 cell migration, and upregulated the protein expression of caspase 3 and cleaved caspase 3 expression, while did not show any inhibition on 293T cells. In vivo orthotopic xenotransplantation model indicated that D-EXO inhibited tumor growth characterized by diminished tumor weight and improved survival rate. No significant change in body weight was observed after the D-EXO treatment. In conclusion, D-EXO proposed in this study could be utilized to treat LUAD with lung-specific delivery effects to improve the survival rate.
    Keywords:  doxorubicin; exosomes; lung adenocarcinoma; treatment
    DOI:  https://doi.org/10.1002/biot.202300296