bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2024–08–11
nine papers selected by
Muhammad Rizwan, COMSATS University
  1. Exosomes: Emerging Insights into the Progression of Pancreatic Cancer.
  2. Harnessing exosomes as cancer biomarkers in clinical oncology.
  3. Gastric cancer cell-derived exosomal miR-541-5p induces M2 macrophage polarization through DUSP3/JAK2/STAT3 pathway.
  4. Exosomal CircRNAs: A Future Star in Colorectal Cancer.
  5. Leveraging the intratumoral microbiota to treat human cancer: are engineered exosomes an effective strategy?
  6. Diagnostic and screening potential of plasma exosome miR‑99b‑5p and its combination with other miRNAs for colorectal cancer.
  7. Exosomes: Methods for Isolation and Characterization in Biological Samples.
  8. Plasma-derived exosomal long noncoding RNAs of pancreatic cancer patients as novel blood-based biomarkers of disease.
  9. Exosomes Isolation, Purification, and Characterization.
  1. Int J Biol Sci. 2024 ;20(10): 4098-4113
    Exosomes: Emerging Insights into the Progression of Pancreatic Cancer.
    Xulin Zhou, Yongmin Yan, Ye Shen, Min Xu, Wenrong Xu.
      Pancreatic cancer is a very aggressive and fatal malignancy with few therapeutic choices and a poor prognosis. Understanding the molecular pathways that drive its growth is critical for developing effective therapeutic strategies. Exosomes, small extracellular vesicles secreted by numerous cell types, have recently emerged as essential intercellular communication mediators, with implications for tumor growth and metastasis. In this article, we present a review of current knowledge about exosomes and their role in pancreatic cancer progression We discuss the biogenesis and characteristics of exosomes, as well as their cargo and functional significance in tumor growth, immune evasion, angiogenesis, invasion, and metastasis. We further emphasize the potential of exosomes as diagnostic biomarkers and therapeutic targets for pancreatic cancer. Finally, we discuss the challenges and future perspectives in using exosomes to improve patient outcomes in pancreatic cancer.
    Keywords:  biomarker; exosomes; pancreatic cancer; progression
    DOI:  https://doi.org/10.7150/ijbs.97076
  2. Cancer Cell Int. 2024 Aug 07. 24(1): 278
    Harnessing exosomes as cancer biomarkers in clinical oncology.
    Subhrojyoti Ghosh, Ramya Lakshmi Rajendran, Atharva A Mahajan, Ankita Chowdhury, Aishi Bera, Sudeepta Guha, Kashmira Chakraborty, Rajanyaa Chowdhury, Aritra Paul, Shreya Jha, Anuvab Dey, Amit Dubey, Sukhamoy Gorai, Purbasha Das, Chae Moon Hong, Anand Krishnan, Prakash Gangadaran, Byeong-Cheol Ahn.
      Exosomes are extracellular vesicles well known for facilitating cell-to-cell communication by distributing essential macromolecules like proteins, DNA, mRNA, lipids, and miRNA. These vesicles are abundant in fluids distributed throughout the body, including urine, blood, saliva, and even bile. They are important diagnostic tools for breast, lung, gastrointestinal cancers, etc. However, their application as cancer biomarkers has not yet been implemented in most parts of the world. In this review, we discuss how OMICs profiling of exosomes can be practiced by substituting traditional imaging or biopsy methods for cancer detection. Previous methods like extensive imaging and biopsy used for screening were expensive, mostly invasive, and could not easily provide early detection for various types of cancer. Exosomal biomarkers can be utilized for routine screening by simply collecting body fluids from the individual. We anticipate that the use of exosomes will be brought to light by the success of clinical trials investigating their potential to enhance cancer detection and treatment in the upcoming years.
    Keywords:  Cancer biomarkers; Cancer diagnosis; Clinical signature; Diagnostic tool; Exosomes; Molecular profiling; Prognostic indicator; Tumor-derived exosomes
    DOI:  https://doi.org/10.1186/s12935-024-03464-5
  3. BMC Cancer. 2024 Aug 06. 24(1): 957
    Gastric cancer cell-derived exosomal miR-541-5p induces M2 macrophage polarization through DUSP3/JAK2/STAT3 pathway.
    Haimin Xiao, Jia Fu, Ruiting Liu, Likun Yan, Zheqi Zhou, Jinyan Yuan.
       PURPOSE: Exosomal microRNAs have been identified as important mediators of communication between tumor cells and macrophages in the microenvironment. miR-541-5p was reported to be involved in hepatocellular carcinoma progression, but its role in gastric cancer (GC) and in GC cell-macrophage crosstalk is unknown.
    METHODS: Cell proliferation, migration and invasion were respectively assessed by CCK-8 assay, scratch and Transwell assays. RT-qPCR was used to detect the level of miR-541-5p, macrophage markers and DUSP3. The percentage of CD11b+CD206+ cell population was analyzed by flow cytometry. Western blotting was employed to evaluate DUSP3-JAK2/STAT3 pathway proteins and exosome markers. The interaction between miR-541-5p and DUSP3 was verified by luciferase assay.
    RESULTS: The results showed that miR-541-5p was upregulated in GC tissues and cells, and stimulated GC cell growth, migration and invasion in vitro. GC cells induce M2 macrophage polarization by secreting the exosomal miR-541-5p. Exosomal miR-541-5p maintained JAK2/STAT3 pathway activation in macrophages by targeting negative regulation of DUSP3. Inhibiting miR-541-5p significantly limited tumor growth in vivo.
    CONCLUSION: In conclusion, miR-541-5p promotes GC cell progression. GC cells may induce macrophage M2 polarization through the exosomal miR-541-5p-mediated DUSP3/JAK2/STAT3 pathway. miR-541-5p may be a potential therapeutic target for GC.
    Keywords:  DUSP3; Exosome; Gastric cancer; JAK2/STAT3 pathway; Macrophage polarization; miR-541-5p
    DOI:  https://doi.org/10.1186/s12885-024-12672-1
  4. Curr Cancer Drug Targets. 2024 Aug 06.
    Exosomal CircRNAs: A Future Star in Colorectal Cancer.
    Yuanzhi Zhou, Chengyan Wei, Yuqi Xu, Jingjing Wang, Chunwei Zhang, Yong Jin.
      Colorectal cancer (CRC) is currently the third most common malignancy world-wide, with an increasing mortality rate and treatment resistance. Due to the lack of effective biomarkers and therapeutic targets, the early diagnosis and treatment of colorectal cancer re-main suboptimal. Circular RNAs (circRNAs) are a novel class of non-coding RNAs with co-valent closed-loop structures that are well stabilized and conserved and are involved in multi-ple pathological conditions in humans. CircRNAs have been identified to be enriched and sta-ble in exosomes. In addition, there is growing proof that exosomal circRNAs that have been identified as oncogenes or tumor suppressors regulate CRC growth, migration, and sensitivity to radiotherapy and chemotherapy. Exosomal circRNAs represent promising candidates as di-agnostic biomarkers and anti-tumor targets. In this article, we explore recent studies on exo-somal circRNAs in CRC and describe their biological functions in colorectal cancer develop-ment, illustrating their potential as biomarkers and targeted therapeutic capabilities.
    Keywords:  Exosome; biomarker; circRNA; colorectal cancer; functions; therapeutic targets.
    DOI:  https://doi.org/10.2174/0115680096323472240710101854
  5. J Transl Med. 2024 Aug 05. 22(1): 728
    Leveraging the intratumoral microbiota to treat human cancer: are engineered exosomes an effective strategy?
    Jie Qiu, Yuancong Jiang, Nanwei Ye, Gan Jin, Hao Shi, Da Qian.
      Cancer remains a leading cause of global mortality. The tumor microbiota has increasingly been recognized as a key regulator of cancer onset and progression, in addition to shaping tumor responses to immunotherapy. Microbes, including viruses, bacteria, fungi, and other eukaryotic species can impact the internal homeostasis and health of humans. Research focused on the gut microflora and the intratumoral microbiome has revolutionized the current understanding of how tumors grow, progress, and resist therapeutic interventions. Even with this research, however, there remains relatively little that is known with respect to the abundance of microbes and their effects on tumors and the tumor microenvironment. Engineered exosomes are a class of artificial extracellular nanovesicles that can actively transport small molecule drugs and nucleic acids, which have the broad prospects of tumor cell therapy. The present review offers an overview of recent progress and challenges associated with the intratumoral microbiome and engineered exosomes in the context of cancer research. These discussions are used to inform the construction of a novel framework for engineered exosome-mediated targeted drug delivery, taking advantage of intratumoral microbiota diversity as a strategic asset and thereby providing new opportunities to more effectively treat and manage cancer in the clinic.
    Keywords:  Cancer; Engineering exosomes; Intratumoral Microbiota; Treatment; Tumor microenvironment
    DOI:  https://doi.org/10.1186/s12967-024-05531-x
  6. Oncol Lett. 2024 Oct;28(4): 461
    Diagnostic and screening potential of plasma exosome miR‑99b‑5p and its combination with other miRNAs for colorectal cancer.
    Chang Zhang, Limei Zhang, Qiyuan Huang, Siyuan Jiang, Tao Peng, Shu Wang, Xuehu Xu.
      Extracellular vesicles (EVs) secreted by tumor cells have been documented to hold viable biomarker potential. Therefore, the present study evaluated the potential clinical value of EV-microRNAs (miRNAs or miRs) in the plasma exosomes of patients with colorectal cancer (CRC) for the early diagnosis and screening of CRC. In total, 95 plasma samples were collected at The Third Affiliated Hospital of Guangzhou Medical University (Guangzhou, China) between 2017 and 2019. Specifically, 68 samples were from patients with CRC and 27 were from healthy control (HC) donors. High-throughput sequencing was used to detect the expression of miRNAs in the isolated plasma EVs, which was subsequently verified by reverse transcription-quantitative PCR. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic potential of single and combined miRNAs for CRC. Bioinformatics analysis was employed to predict the target genes of candidate miRNAs. Compared with those in the HC group, the CRC group expressed higher levels of miR-99b-5p and miR-409-3p, especially during the early stages of CRC. Clinicopathological analysis confirmed the higher expression levels of miR-99b-5p during the early stages, as well as higher expression levels in the colon compared with those in the rectum. ROC curve analysis revealed that the area under the curve (AUC) of miR-99b-5p for the diagnosis of early CRC was 73.5% (P=0.007). The early diagnostic capability of miR-99b-5p combined with miR-409-3p for CRC was evaluated, and the AUC was found to be 74.1% (P=0.006). In addition, the AUC of the combination of miR-99b-5p, miR-409-3p and carcinoembryonic antigen was 81.2% (P<0.001), indicating that this three-parameter combination displayed higher diagnostic power compared with any single miRNA for early CRC screening. The results from the present study suggest that the expression of miR-99b-5p in plasma exosomes is significantly upregulated in CRC, which holds potential for the early diagnosis of this cancer type. Such potential can be enhanced further by combining it with other miRNAs. Therefore, the present study provides a comprehensive but preliminary insight for the viability of miR-99b-5p (alone or combined with other miRNAs) for CRC diagnosis, which requires further exploration in the future.
    Keywords:  colorectal cancer; early diagnosis; microRNA-409-3p; microRNA-99b-5p; plasma exosomes
    DOI:  https://doi.org/10.3892/ol.2024.14594
  7. Methods Mol Biol. 2024 ;2835 181-213
    Exosomes: Methods for Isolation and Characterization in Biological Samples.
    Sarojini Singh, Cassidy Dansby, Divyanshi Agarwal, Purnima Devaki Bhat, Praveen Kumar Dubey, Prasanna Krishnamurthy.
      Exosomes are small lipid bilayer-encapsulated nanosized extracellular vesicles of endosomal origin. Exosomes are secreted by almost all cell types and are a crucial player in intercellular communication. Exosomes transmit cellular information from donor to recipient cells in the form of proteins, lipids, and nucleic acids and influence several physiological and pathological responses. Due to their capacity to carry a variety of cellular cargo, low immunogenicity and cytotoxicity, biocompatibility, and ability to cross the blood-brain barrier, these nanosized vesicles are considered excellent diagnostic tools and drug-delivery vehicles. Despite their tremendous potential, the progress in therapeutic applications of exosomes is hindered by inadequate isolation techniques, poor characterization, and scarcity of specific biomarkers. The current research in the field is focused on overcoming these limitations. In this chapter, we have reviewed conventional exosome isolation and characterization methods and recent advancements, their advantages and limitations, persistent challenges in exosome research, and future directions.
    Keywords:  Exosome characterization; Exosome isolation; Exosomes; Extracellular vesicles; Intercellular communication
    DOI:  https://doi.org/10.1007/978-1-0716-3995-5_17
  8. BMC Cancer. 2024 Aug 06. 24(1): 961
    Plasma-derived exosomal long noncoding RNAs of pancreatic cancer patients as novel blood-based biomarkers of disease.
    Xiaomeng He, Litian Chen, Yang Di, Wenyang Li, Xin Zhang, Zhihui Bai, Zhefeng Wang, Shanshan Liu, Christopher Corpe, Jin Wang.
       BACKGROUND: Pancreatic cancer (PaCa) is one of the most intractable and fatal malignancies and is associated with the dysregulation of long noncoding RNAs (lncRNAs), which are a large class of noncoding RNAs larger than 200 nt that act as competing endogenous RNAs or sponges for miRNAs to induce tumour biological behaviours. However, their clinical value in treating pancreatic cancer has been poorly explained, but they are essential for improving the prognosis of PaCa patients.
    METHODS: We analysed the plasma-derived exosomal lncRNA profiles of PaCa patients by using whole-transcriptome sequencing analysis and identified significantly differentially expressed lncRNAs, including LINC01268, LINC02802, AC124854.1, and AL132657.1. In the current study, the expression levels of four plasma-derived exosomal lncRNAs in PaCa plasma were validated via quantitative real-time polymerase chain reaction (qRT‒PCR). The relationship between the expression of the four lncRNAs and the clinicopathological features of patients with PaCa was also evaluated.
    RESULTS: We demonstrated that exosomal LINC01268, LINC02802, AC124854.1 and AL132657.1 were highly expressed in PaCa plasma compared with those in normal controls; moreover, they were positively correlated with the serum expression of carbohydrate antigen 19-9 (CA19-9). The receiver operating characteristic curves (AUCs) of the four lncRNAs were 0.8421, 0.6544, 0.7190, and 0.6321, and the AUC value of the combination of the four exosomal lncRNAs increased to 0.8476, with a sensitivity of 0.72 and specificity of 0.89. These results suggested that the plasma-derived exosomal genes LINC01268, LINC02802, AC124854.1, and AL132657.1 may be novel diagnostic markers for PaCa.
    CONCLUSIONS: Our research demonstrated that the plasma-derived exosomal lncRNAs of PaCa patients are novel blood-based biomarkers of disease.
    Keywords:  Biomarker; Diagnosis; Exosome; Long noncoding RNA; Pancreatic cancer
    DOI:  https://doi.org/10.1186/s12885-024-12755-z
  9. Methods Mol Biol. 2024 ;2835 173-180
    Exosomes Isolation, Purification, and Characterization.
    Prabhat Ranjan, Suresh Kumar Verma.
      Exosomes are double-layered lipid membranous nanovesicles that are endosomal in origin and secreted by almost all cells. They are 30-130 nm in size and contain various molecular signatures such as miRNAs, mRNAs, DNA, lipids, and proteins. Due to their highly heterogeneous content, exosomes have a major role in influencing cellular physiology and pathology. Although exosome research has been in progress for a long time, its biomedical applications have recently been expanding due to its bio-friendly nature. However, the most challenging part is its isolation to obtain quality exosomes with good yield. Therefore, in this chapter, we have described appropriate protocols for exosome isolation and characterization along with alternative purification methods.
    Keywords:  Bone marrow-progenitor cells; Endothelial cells; Exosomes; Fibroblasts; Sucrose density gradient; Ultracentrifugation
    DOI:  https://doi.org/10.1007/978-1-0716-3995-5_16
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