bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2024–05–12
six papers selected by
Muhammad Rizwan, COMSATS University



  1. Heliyon. 2024 May 15. 10(9): e30328
      As one of the deadliest gynaecological cancers, ovarian cancer has been on the list. With lesser-known symptoms and lack of an accurate detection method, it is still difficult to catch it early. In terms of both the diagnosis and outlook for cancer, liquid biopsy has come a long way with significant advancements. Exosomes, extracellular components commonly shed by cancerous cells, are nucleic acid-rich particles floating in almost all body fluids and hold enormous promise, leading to minimallyinvasive molecular diagnostics. They have been shown as potential biomarkers in liquid biopsy, being implicated in tumour growth and metastasis. In order to address the drawbacks of ovarian cancer tumor heterogeneity, a liquid biopsy-based approach is being investigated by detecting cell-free nucleic acids, particularly non-coding RNAs, having the advantage of being less invasive and more prominent in nature. microRNAs are known to actively contribute to cancer development and their existence inside exosomes has also been made quite apparent which can be leveraged to diagnose and treat the disease. Extraction of miRNAs and exosomes is an arduous execution, and while other approaches have been investigated, none have produced results that are as encouraging due to limits in time commitment, yield, and, most significantly, damage to the exosomal structure resulting discrepancies in miRNA-based expression profiling for disease diagnosis. We have briefly outlined and reviewed the difficulties with exosome isolation techniques and the need for their standardization. The several widely used procedures and their drawbacks in terms of the exosomal purity they may produce have also been outlined.
    Keywords:  Exosomes; Isolation; Liquid biopsy; Ovarian cancer; microRNA
    DOI:  https://doi.org/10.1016/j.heliyon.2024.e30328
  2. Int J Biol Sci. 2024 ;20(7): 2388-2402
      Metastasis is the leading cause of death in colorectal cancer (CRC) patients. By mediating intercellular communication, exosomes exhibit considerable value in regulating tumor metastasis. Long non-coding RNAs (lncRNAs) are abundant in exosomes and participate in regulating tumor progression. However, it is poorly understood how the cancer-secreted exosomal lncRNAs affect CRC proliferation and metastasis. Here, by analyzing the public databases we identified a lncRNA SNHG3 and demonstrated that SNHG3 was delivered through CRC cells-derived exosomes to promote metastasis in CRC. Mechanistically, exosomal SNHG3 was internalized by CRC cells and afterward upregulated the expression of β-catenin by facilitating the intranuclear transport of hnRNPC. Consequently, the RNA stability of β-catenin was enhanced which led to the activation of EMT and metastasis of CRC cells. Our findings expand the oncogenic mechanisms of exosomal SNHG3 and identify it as a diagnostic marker for CRC.
    Keywords:  colorectal cancer; exosome; lncRNA; metastasis
    DOI:  https://doi.org/10.7150/ijbs.88313
  3. Transl Gastroenterol Hepatol. 2024 ;9 29
      Pancreatic cancer (PC) is a lethal disease that presents a considerable challenge to healthcare providers and patients, given its low survival rate. However, recent advancements in precision medicine and innovative technologies have transformed the management of this disease. Among these advancements, extracellular vesicles (EVs) have emerged as crucial players in cancer progression. In PC, EVs play a pivotal role by facilitating cell-cell communication, impeding immune response, promoting cancer cell proliferation and survival, and supporting angiogenesis and chemoresistance. Cancer-derived EVs have a distinct oncogenic composition supporting tumour development and progression. Hence, they are critical biomarker candidates for various cancers, including PC. Notably, EVs can be isolated from diverse biological fluids such as blood, urine, and saliva, making them an ideal minimally invasive diagnostic and monitoring tool for PC patients. Despite the promising findings in the field of EVs, clinical validation as biomarkers is lacking. Furthermore, EVs being biocompatible, can act as drug carriers, delivering therapeutic molecules directly to cancer cells while minimizing toxicity to healthy cells. Therefore, understanding the role of EVs as biomarkers and their potential as drug cargo vehicles may revolutionise early detection, prognostication, and treatment in cancer. This mini-review summarises the latest understanding of their role in intercellular communication, involvement as potential biomarkers and drug carriers.
    Keywords:  Extracellular vesicles (EVs); pancreatic cancer (PC); precision medicine
    DOI:  https://doi.org/10.21037/tgh-23-53
  4. iScience. 2024 Apr 19. 27(4): 109506
      It is imperative to explore biomarkers that are both precise and readily accessible in the comprehensive management of breast cancer. A multicenter cohort, including 512 breast cancer patients and 198 nonneoplastic individuals, was recruited to detect the level of tumor-derived extracellular vesicles using our method based on dual DNA tetrahedral nanostructures. The level of tumor-derived extracellular vesicles was significantly higher in newly diagnosed breast cancer patients than in nonneoplastic individuals at a cutoff value of 3.58 U/μL. For postoperative metastasis monitoring, the level of tumor-derived extracellular vesicles was significantly higher in breast cancer patients with metastasis than in those without metastasis at a cutoff value of 3.91 U/μL. Its efficacy of diagnosis and metastasis monitoring was superior to traditional tumor markers. Elevated level of tumor-derived extracellular vesicles served as a predictive biomarker for diagnosis and metastasis monitoring in breast cancer patients.
    Keywords:  Functional aspects of cell biology; Oncology
    DOI:  https://doi.org/10.1016/j.isci.2024.109506
  5. Front Immunol. 2024 ;15 1395332
      PD-1/PD-L1 signaling is a key factor of local immunosuppression in the tumor microenvironment. Immune checkpoint inhibitors targeting PD-1/PD-L1 signaling have achieved tremendous success in clinic. However, several types of cancer are particularly refractory to the anti-PD-1/PD-L1 treatment. Recently, a series of studies reported that IFN-γ can stimulate cancer cells to release exosomal PD-L1 (exoPD-L1), which possesses the ability to suppress anticancer immune responses and is associated with anti-PD-1 response. In this review, we introduce the PD-1/PD-L1 signaling, including the so-called 'reverse signaling'. Furthermore, we summarize the immune treatments of cancers and pay more attention to immune checkpoint inhibitors targeting PD-1/PD-L1 signaling. Additionally, we review the action mechanisms and regulation of exoPD-L1. We also introduce the function of exoPD-L1 as biomarkers. Finally, we review the methods for analyzing and quantifying exoPD-L1, the therapeutic strategies targeting exoPD-L1 to enhance immunotherapy and the roles of exoPD-L1 beyond cancer. This comprehensive review delves into recent advances of exoPD-L1 and all these findings suggest that exoPD-L1 plays an important role in both cancer and other fields.
    Keywords:  PD-L1; biomarker; exosomal PD-L1; exosome; immune checkpoint; immunotherapy; resistance
    DOI:  https://doi.org/10.3389/fimmu.2024.1395332
  6. Am J Cancer Res. 2024 ;14(4): 1904-1913
      Addressing the critical challenge of early ovarian cancer (OC) detection, our study focuses on identifying novel biomarkers by analyzing preoperative peripheral blood exosomes from high-grade serous ovarian cancer (HGSC) patients and healthy controls. Utilizing high-performance liquid chromatography-mass spectrometry-based quantitative proteomics, we isolated and analyzed peripheral blood exosomes to identify differentially expressed proteins (DEPs). This comprehensive analysis, supported by gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) database assessments, revealed 28 proteins with decreased abundance and 33 with increased abundance in HGSC patients compared to controls. Notably, Zinc Finger Protein 587B (ZNF587B) exhibited a significant reduction in abundance, confirmed by decreased mRNA and protein levels in HGSC and normal ovarian tissues, consistent with omes exosomal protein expression levels. Immunohistochemical staining further confirmed reduced ZNF587B protein levels in HGSC tissues. The significant correlation between ZNF587B expression levels and tumor stage underscores its potential as a valuable biomarker for early liquid biopsy screening of OC. Our findings suggest ZNF587B plays a crucial role in early HGSC detection, highlighting the importance of further research to validate its clinical utility and improve ovarian cancer patient outcomes.
    Keywords:  Ovarian cancer; ZNF587B; exosomes; liquid biopsy
    DOI:  https://doi.org/10.62347/RBTM1834