bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2023–04–16
six papers selected by
Muhammad Rizwan, COMSATS University
  1. Exosomes: a potential diagnostic and treatment modality in the quest for counteracting cancer.
  2. The Role of Exosomes in Epithelial-to-Mesenchymal Transition and Cell Functional Properties in Head and Neck Cancer.
  3. Exosomal miRNAs in the Tumor Microenvironment of Multiple Myeloma.
  4. From Exosome Biogenesis to Absorption: Key Takeaways for Cancer Research.
  5. RNA profile of immuno-magnetically enriched lung cancer associated exosomes isolated from clinical samples.
  6. Exosomal miRNAs as novel avenues for breast cancer treatment.
  1. Cell Oncol (Dordr). 2023 Apr 11.
    Exosomes: a potential diagnostic and treatment modality in the quest for counteracting cancer.
    Gayatri Patel, Tejas Girish Agnihotri, Manoj Gitte, Tanuja Shinde, Shyam Sudhakar Gomte, Roshan Goswami, Aakanchha Jain.
       BACKGROUND: Exosomes are nanosized bio vesicles formed when multivesicular bodies and the plasma membrane merge and discharge into bodily fluids. They are well recognized for facilitating intercellular communication by transporting numerous biomolecules, including DNA, RNAs, proteins, and lipids, and have been implicated in varied diseases including cancer. Exosomes may be altered to transport a variety of therapeutic payloads, including as short interfering RNAs, antisense oligonucleotides, chemotherapeutic drugs, and immunological modulators, and can be directed to a specific target. Exosomes also possess the potential to act as a diagnostic biomarker in cancer, in addition to their therapeutic potential.
    CONCLUSION: In this review, the physiological roles played by exosomes were summarized along with their biogenesis process. Different isolation techniques of exosomes including centrifugation-based, size-based, and polymer precipitation-based techniques have also been described in detail with a special focus on cancer therapeutic applications. The review also shed light on techniques of incubation of drugs with exosomes and their characterization methods covering the most advanced techniques. Myriad applications of exosomes in cancer as diagnostic biomarkers, drug delivery carriers, and chemoresistance-related issues have been discussed at length. Furthermore, a brief overview of exosome-based anti-cancer vaccines and a few prominent challenges concerning exosomal delivery have been concluded at the end.
    Keywords:  Biogenesis; Biomarkers; Exosomes; Isolation; cancer
    DOI:  https://doi.org/10.1007/s13402-023-00810-z
  2. Cancers (Basel). 2023 Apr 05. pii: 2156. [Epub ahead of print]15(7):
    The Role of Exosomes in Epithelial-to-Mesenchymal Transition and Cell Functional Properties in Head and Neck Cancer.
    Nicholas S Mastronikolis, Efthymios Kyrodimos, Despoina Spyropoulou, Alexander Delides, Evangelos Giotakis, Zoi Piperigkou, Nikos K Karamanos.
      Exosomes are nanosized vesicles that are produced in normal and cancer cells, promoting intracellular communication. In head and neck cancer (HNC), exosomes are involved in many undesirable events of cancer development and progression, including angiogenesis, tumor microenvironment (TME) remodeling, invasion, epithelial-to-mesenchymal transition (EMT), metastasis, extracellular matrix (ECM) degradation, and drug resistance. Exosomes are involved in altering the signaling pathways in recipient cells by the cargoes they carry. Proteins, lipids, and nucleic acids such as DNA fragments and RNAs (i.e., mRNAs, miRNAs, and long non-coding RNAs) are carried in the exosomes to promote cell communication. EMT is a critical cellular process in which epithelial cells are forced to become mesenchymal cells by the actions of SNAIL/SLUG, TWIST, and ZEB family transcription factors carried in exosomes that facilitate metastasis. In this critical review, we focused on exosome biogenesis, their cargoes, and their involvement in EMT induction and metastasis during HNC. Insights into exosome isolation and characterization, as well as their key role in ECM remodeling and degradation, are also presented and critically discussed. More importantly, this article addresses the role of exosomes in HNC and drug resistance induced in drug-sensitive cancer cells. In addition, exosomes have a great potential to be used as diagnostic and therapeutic tools. A better understanding on exosome biogenesis, composition, and functions in HNC will aid in developing novel therapeutic strategies to treat HNC, overcome therapy resistance, and avoid metastasis, which is a significant cause of cancer death.
    Keywords:  drug resistance; epithelial-to-mesenchymal transition; exosomes; extracellular matrix; head and neck cancer; metastasis
    DOI:  https://doi.org/10.3390/cancers15072156
  3. Cells. 2023 Mar 28. pii: 1030. [Epub ahead of print]12(7):
    Exosomal miRNAs in the Tumor Microenvironment of Multiple Myeloma.
    Shamila D Alipoor, Hong Chang.
      Multiple myeloma (MM) is a malignancy of plasma cells in the bone marrow and is characterized by the clonal proliferation of B-cells producing defective monoclonal immunoglobulins. Despite the latest developments in treatment, drug resistance remains one of the major challenges in the therapy of MM. The crosstalk between MM cells and other components within the bone marrow microenvironment (BME) is the major determinant of disease phenotypes. Exosomes have emerged as the critical drivers of this crosstalk by allowing the delivery of informational cargo comprising multiple components from miniature peptides to nucleic acids. Such material transfers have now been shown to perpetuate drug-resistance development and disease progression in MM. MicroRNAs(miRNAs) specifically play a crucial role in this communication considering their small size that allows them to be readily packed within the exosomes and widespread potency that impacts the developmental trajectory of the disease inside the tumor microenvironment (TME). In this review, we aim to provide an overview of the current understanding of the role of exosomal miRNAs in the epigenetic modifications inside the TME and its pathogenic influence on the developmental phenotypes and prognosis of MM.
    Keywords:  drug resistance; exosomal miRNA; exosome; multiple myeloma
    DOI:  https://doi.org/10.3390/cells12071030
  4. Cancers (Basel). 2023 Mar 27. pii: 1992. [Epub ahead of print]15(7):
    From Exosome Biogenesis to Absorption: Key Takeaways for Cancer Research.
    Nicolas Cheuk Hang Lau, Judy Wai Ping Yam.
      Exosomes are mediators of intercellular communication in normal physiology and diseases. While many studies have emerged on the function of exosomal cargoes, questions remain regarding the origin of these exosomes. The packaging and secretion of exosomes in different contexts modify exosomal composition, which may in turn impact delivery, uptake and cargo function in recipient cells. A mechanistic understanding of exosome biology is therefore crucial to investigating exosomal function in complex biological systems and to the development of novel therapeutic approaches. Here, we outline the steps in exosome biogenesis, including endosome formation, MVB formation, cargo sorting and extracellular release, as well as exosome absorption, including targeting, interaction with recipient cells and the fate of internalized exosomes. In addition to providing a framework of exosome dynamics, we summarize current evidence on major pathways and regulatory mechanisms. We also highlight the various mechanisms observed in cancer and point out directions to improve study design in exosome biology. Further research is needed to illuminate the relationship between exosome biogenesis and function, which will aid the development of translational applications.
    Keywords:  biogenesis; cancer; endocytosis; exosome; extracellular vesicle; intercellular communication; regulation; targeting
    DOI:  https://doi.org/10.3390/cancers15071992
  5. Cancer Genet. 2023 Mar 29. pii: S2210-7762(23)00022-4. [Epub ahead of print]274-275 59-71
    RNA profile of immuno-magnetically enriched lung cancer associated exosomes isolated from clinical samples.
    Shefali Singh, Deevanshu Goyal, Karthikeyan Raman, Sachin Kumar, Prabhat Singh Malik, Ravikrishnan Elangovan.
      Exosomal cargo secreted from cancer cells has been associated with the development and progression of the tumour. Enriching clinically relevant tissue-specific exosomes may assist in the focused analysis of RNA molecules packaged during cancer. Therefore, this study utilized a rapid immunomagnetic enrichment approach for targeted isolation of lung cancer cell-derived exosomes from human plasma, followed by analysing their cargo RNA using high throughput sequencing. The total RNA purified from these immunomagnetically enriched exosomes provided adequate RNA quality for characterization through the Illumina platform. Differential expression analysis was performed between patients and healthy controls to study the altered exosomal RNA profile during lung cancer. Further, functional enrichment analysis was performed with the list of identified differentially expressed genes (DEGs). In total, 1383 mRNAs and 64 lncRNA were identified as differentially expressed between patient plasma exosomes than healthy controls (fold change > 2, P < 0.05). Kyoto encyclopaedia of Genes and Genomes (KEGG) pathway analysis revealed that the DEGs were mainly associated with cancer-related pathways, purine metabolism, calcium, and cGMP-PKG signalling pathways. In conclusion, the presented approach successfully demonstrated a novel strategy for focused disease-specific transcriptome analysis, which provides a feasible option for identifying disease-specific exosome biomarkers for detecting non-small lung cancer.
    Keywords:  Illumina HiSeq; Immunomagnetic capture; Liquid biopsy; LncRNAs; Tissue specific exosome enrichment; Total transcriptome sequencing
    DOI:  https://doi.org/10.1016/j.cancergen.2023.03.008
  6. Front Genet. 2023 ;14 1134779
    Exosomal miRNAs as novel avenues for breast cancer treatment.
    Tejveer Singh, Mahesh Kaushik, Lokesh Chandra Mishra, Chesta Behl, Vijay Singh, Hardeep Singh Tuli.
      Breast cancer is the most commonly diagnosed cancer and a leading cause of death in women worldwide. It is a heterogeneous disease, as shown by the gene expression profiles of breast cancer samples. It begins in milk-producing ducts, with a high degree of diversity between and within tumors, as well as among cancer-bearing individuals. The enhanced prevalence of breast cancer is influenced by various hormonal, lifestyle, and environmental factors, and very early onset of the disease correlates strongly with the risk of local and distant recurrence. Many subtypes are difficult to treat with conventional therapeutic modalities, and therefore, optimal management and early diagnosis are the first steps to minimizing the mortality linked with breast cancer. The use of newer methods of nanotechnology extends beyond the concept of synthesizing drug delivery mechanisms into the creation of new therapeutics, such as delivering chemotherapeutics with nanomaterial properties. Exosomes, a class of nanovesicles, are emerging as novel tools for deciphering the patient-specific proteins and biomarkers across different disease models, including breast cancer. In this review, we address the role of exosomal miRNA in breast cancer diagnosis and treatment.
    Keywords:  breast cancer; diagnosis; exosome; metastasis; miRNA
    DOI:  https://doi.org/10.3389/fgene.2023.1134779
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