bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2024‒03‒10
twelve papers selected by
Muhammad Rizwan, COMSATS University
  1. Diagnostic potential of exosomal extracellular vesicles in oncology.
  2. [Advances in salivary exosomal miRNAs in head and neck squamous carcinoma].
  3. Diagnostic value of plasma-derived exosomal miR-223 for epithelial ovarian cancer.
  4. Investigating the Effects of Chordoma Cell-Derived Exosomes on the Tumorigenicity of Nucleus Pulposus Cells.
  5. Exosome-mediated communication between gastric cancer cells and macrophages: implications for tumor microenvironment.
  6. Exosomal microRNAs in breast cancer: towards theranostic applications.
  7. Unlocking the potential of exosomes in cancer research: A paradigm shift in diagnosis, treatment, and prevention.
  8. Smart exosomes enhance PDAC targeted therapy.
  9. Exosomal lncRNA XIST promotes perineural invasion of pancreatic cancer cells via miR-211-5p/GDNF.
  10. Exosomes as Powerful Biomarkers in Cancer: Recent Advances in Isolation and Detection Techniques.
  11. Exosome circATP8A1 induces macrophage M2 polarization by regulating the miR-1-3p/STAT6 axis to promote gastric cancer progression.
  12. Extracellular vesicles as a promising source of lipid biomarkers for breast cancer detection in blood plasma.
  1. BMC Cancer. 2024 Mar 08. 24(1): 322
    Diagnostic potential of exosomal extracellular vesicles in oncology.
    Mickensone Andre, Allen Caobi, Jana S Miles, Arti Vashist, Marco A Ruiz, Andrea D Raymond.
      Liquid biopsy can detect circulating cancer cells or tumor cell-derived DNA at various stages of cancer. The fluid from these biopsies contains extracellular vesicles (EVs), such as apoptotic bodies, microvesicles, exomeres, and exosomes. Exosomes contain proteins and nucleic acids (DNA/RNA) that can modify the microenvironment and promote cancer progression, playing significant roles in cancer pathology. Clinically, the proteins and nucleic acids within the exosomes from liquid biopsies can be biomarkers for the detection and prognosis of cancer. We review EVs protein and miRNA biomarkers identified for select cancers, specifically melanoma, glioma, breast, pancreatic, hepatic, cervical, prostate colon, and some hematological malignancies. Overall, this review demonstrates that EV biomolecules have great potential to expand the diagnostic and prognostic biomarkers used in Oncology; ultimately, EVs could lead to earlier detection and novel therapeutic targets. Clinical implicationsEVs represent a new paradigm in cancer diagnostics and therapeutics. The potential use of exosomal contents as biomarkers for diagnostic and prognostic indicators may facilitate cancer management. Non-invasive liquid biopsy is helpful, especially when the tumor is difficult to reach, such as in pancreatic adenocarcinoma. Moreover, another advantage of using minimally invasive liquid biopsy is that monitoring becomes more manageable. Identifying tumor-derived exosomal proteins and microRNAs would allow a more personalized approach to detecting cancer and improving treatment.
    Keywords:  Biomarkers; Cancer; Daignostics; Exosomes; Extracellular vesicles; MicroRNA; Therapeutics
    DOI:  https://doi.org/10.1186/s12885-024-11819-4
  2. Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2024 Mar;38(3): 261-266
    [Advances in salivary exosomal miRNAs in head and neck squamous carcinoma].
    Jinyi He, Liu Yang.
       Salivary exosomes are extracellular vesicles of 30-150 nm in diameter that exist in saliva and play an important role in substance exchange and signal transduction between cells, delivering the lipids, proteins and nucleic acids they carry to the recipient cells and regulating the physiological and pathological processes of the recipient cells. miRNA, as an important "cargo" in exosomes, is transported to the recipient cells and regulates the signaling pathways of the recipient cells, thus playing a regulatory role in disease progression. The miRNAs are transported to the recipient cells and regulate the signaling pathways of the recipient cells, thus playing a regulatory role in the progression of diseases. With the development of technological tools this year, numerous studies have revealed the important role of salivary exosomal miRNAs in the development of head and neck squamous carcinoma and the role of salivary exosomal miRNAs in the diagnosis and treatment of head and neck squamous carcinoma. This paper reviews the occurrence, treatment and prognosis of salivary exosomal miRNA in head and neck squamous carcinoma, and discusses the potential prospects and importance of salivary exosomal miRNA as a biomarker in the diagnosis of head and neck squamous carcinoma.
    Keywords:  biomarkers; extracellular vesicles; head and neck squamous carcinoma; salivary exosomes
    DOI:  https://doi.org/10.13201/j.issn.2096-7993.2024.03.016
  3. BMC Womens Health. 2024 Mar 02. 24(1): 150
    Diagnostic value of plasma-derived exosomal miR-223 for epithelial ovarian cancer.
    Li Yang, Zhihong Yang, Zhihui Liu, Na Qi, Lili Tao.
      OBJECTIVES: To evaluate the diagnostic value of plasma exosomal miR-223 and its combination with CA125 for the diagnosis of early-stage epithelial ovarian cancer (EOC).PATIENTS AND METHODS: Exosomes derived from the plasma of 78 EOC patients, 40 patients with epithelial benign ovarian tumors, and 52 healthy participants were isolated using the ultracentrifugation method and identified by transmission electron microscopy (TEM) and western blot.
    RESULTS: The expression of exosomal miR-223 was significantly upregulated in the plasma of EOC patients compared to that in healthy subjects and patients with benign diseases. The combination of exosomal miR-223 and CA125 from plasma had an equivalent area under the ROC curve (AUC) to CA125 alone for discriminating between EOC and non-EOC cases, including healthy subjects and benign ovarian tumors. However, the AUC value of the combination was 0.944 (95% CI: 0.899-0.990) for differentially diagnosing early-stage EOC from healthy subjects, slightly higher than that of CA125 alone (0.928, 95% CI: 0.875-0.981), with a sensitivity and specificity of 0.9784 and 0.885, respectively.
    CONCLUSION: Our data suggest that plasma exosomal miR-223 can be used as a complement to CA125 to increase the diagnostic power for differentiating early-stage EOC from healthy subjects.
    Keywords:  Diagnosis; Epithelial ovarian cancers; Exosomes; miR-223
    DOI:  https://doi.org/10.1186/s12905-024-02976-6
  4. J Neurol Surg B Skull Base. 2024 Apr;85(2): 161-167
    Investigating the Effects of Chordoma Cell-Derived Exosomes on the Tumorigenicity of Nucleus Pulposus Cells.
    Esra Aydemir, Nur Zübeyda Yılmaz, Ömer Faruk Bayrak, Fikrettin Sahin.
      Objective  Interaction of tumor cells with the surrounding environment is essential for tumor growth and progression that eventually leads to metastasis. Growing evidence shows that extracellular vesicles also known as exosomes play a crucial role in signaling between the tumor and its microenvironment. Tumor-derived exosomes have generally protumorigenic effects such as metastasis, hypoxia, angiogenesis, and epithelial-mesenchymal transition. Methods  In this study, exosomes were isolated from a chordoma cell line, MUG-Chor1, and characterized subsequently. The number of exosomes was determined and introduced into the healthy nucleus pulposus (NP) cells for 140 days. The protumorigenic effects of a chordoma cell line-derived exosomes that initiate the tumorigenesis on NP cells were investigated. The impact of tumor-derived exosomes on various cellular events including cell cycle, migration, proliferation, apoptosis, and viability has been studied by treating NP cells with chordoma cell-line-derived exosomes cells. Results  Upon treatment with exosomes, the NP cells not only gained a chordoma-like morphology but also molecular characteristics such as alterations in the levels of certain gene expressions. The migratory and angiogenic capabilities of NP cells increased after treatment with chordoma-derived exosomes. Conclusion  Based on our findings, we can conclude that exosomes carry information from tumor cells and may exert tumorigenic effects on nontumorous cells.
    Keywords:  chordoma; exosomes; nucleus pulposus cells; tumorigenicity
    DOI:  https://doi.org/10.1055/a-2018-4627
  5. Front Immunol. 2024 ;15 1327281
    Exosome-mediated communication between gastric cancer cells and macrophages: implications for tumor microenvironment.
    Yue Qiu, Guimei Lu, Na Li, Yanyan Hu, Hao Tan, Chengyao Jiang.
      Gastric cancer (GC) is a malignant neoplasm originating from the epithelial cells of the gastric mucosa. The pathogenesis of GC is intricately linked to the tumor microenvironment within which the cancer cells reside. Tumor-associated macrophages (TAMs) primarily differentiate from peripheral blood monocytes and can be broadly categorized into M1 and M2 subtypes. M2-type TAMs have been shown to promote tumor growth, tissue remodeling, and angiogenesis. Furthermore, they can actively suppress acquired immunity, leading to a poorer prognosis and reduced tolerance to chemotherapy. Exosomes, which contain a myriad of biologically active molecules including lipids, proteins, mRNA, and noncoding RNAs, have emerged as key mediators of communication between tumor cells and TAMs. The exchange of these molecules via exosomes can markedly influence the tumor microenvironment and consequently impact tumor progression. Recent studies have elucidated a correlation between TAMs and various clinicopathological parameters of GC, such as tumor size, differentiation, infiltration depth, lymph node metastasis, and TNM staging, highlighting the pivotal role of TAMs in GC development and metastasis. In this review, we aim to comprehensively examine the bidirectional communication between GC cells and TAMs, the implications of alterations in the tumor microenvironment on immune escape, invasion, and metastasis in GC, targeted therapeutic approaches for GC, and the efficacy of potential GC drug resistance strategies.
    Keywords:  exosome; gastric cancer (GC); immune; tumor microenvironment (TME); tumor-associated macrophages (TAMs)
    DOI:  https://doi.org/10.3389/fimmu.2024.1327281
  6. Front Mol Biosci. 2024 ;11 1330144
    Exosomal microRNAs in breast cancer: towards theranostic applications.
    Richa Gulati, Tridip Mitra, Rohan Rajiv, Emilda Judith Ezhil Rajan, Chris Pierret, Elizabeth Ann L Enninga, Rajiv Janardhanan.
      Breast cancer is one of the top two reproductive cancers responsible for high rates of morbidity and mortality among women globally. Despite the advancements in the treatment of breast cancer, its early diagnosis remains a challenge. Recent evidence indicates that despite the adroit use of numerous strategies to facilitate rapid and precision-oriented screening of breast cancer at the community level through the use of mammograms, Fine-needle aspiration cytology (FNAC) and biomarker tracking, no strategy has been unequivocally accepted as a gold standard for facilitating rapid screening for disease. This necessitates the need to identify novel strategies for the detection and triage of breast cancer lesions at higher rates of specificity, and sensitivity, whilst taking into account the epidemiologic and social-demographic features of the patients. Recent shreds of evidence indicate that exosomes could be a robust source of biomaterial for the rapid screening of breast cancer due to their high stability and their presence in body fluids. Increasing evidence indicates that the Exosomal microRNAs- play a significant role in modifying the tumour microenvironment of breast cancers, thereby potentially aiding in the proliferation, invasion and metastasis of breast cancer. In this review, we summarize the role of ExomiRs in the tumour microenvironment in breast cancer. These ExomiRs can also be used as candidate biomarkers for facilitating rapid screening and triaging of breast cancer patients for clinical intervention.
    Keywords:  breast cancer; diagnostic markers; drug resistance; drug sensitivity; exosomal miRNAs
    DOI:  https://doi.org/10.3389/fmolb.2024.1330144
  7. Pathol Res Pract. 2024 Feb 20. pii: S0344-0338(24)00125-0. [Epub ahead of print]255 155214
    Unlocking the potential of exosomes in cancer research: A paradigm shift in diagnosis, treatment, and prevention.
    Saloomeh Khoushab, Mina Hobabi Aghmiuni, Negin Esfandiari, Mohammad Reza Roudaki Sarvandani, Mohsen Rashidi, Afshin Taheriazam, Maliheh Entezari, Mehrdad Hashemi.
      Exosomes, which are tiny particles released by cells, have the ability to transport various molecules, including proteins, lipids, and genetic material containing non-coding RNAs (ncRNAs). They are associated with processes like cancer metastasis, immunity, and tissue repair. Clinical trials have shown exosomes to be effective in treating cancer, inflammation, and chronic diseases. Mesenchymal stem cells (MSCs) and dendritic cells (DCs) are common sources of exosome production. Exosomes have therapeutic potential due to their ability to deliver cargo, modulate the immune system, and promote tissue regeneration. Bioengineered exosomes could revolutionize disease treatment. However, more research is needed to understand exosomes in tumor growth and develop new therapies. This paper provides an overview of exosome research, focusing on cancer and exosome-based therapies including chemotherapy, radiotherapy, and vaccines. It explores exosomes as a drug delivery system for cancer therapy, highlighting their advantages. The article discusses using exosomes for various therapeutic agents, including drugs, antigens, and RNAs. It also examines challenges with engineered exosomes. Analyzing exosomes for clinical purposes faces limitations in sensitivity, specificity, and purification. On the other hand, Nanotechnology offers solutions to overcome these challenges and unlock exosome potential in healthcare. Overall, the article emphasizes the potential of exosomes for personalized and targeted cancer therapy, while acknowledging the need for further research.
    Keywords:  Bioengineering; Cancer; Drug screening; Exosomes; Immune response; Nanoparticles; Personalized therapy
    DOI:  https://doi.org/10.1016/j.prp.2024.155214
  8. J Control Release. 2024 Mar 06. pii: S0168-3659(24)00133-0. [Epub ahead of print]368 413-429
    Smart exosomes enhance PDAC targeted therapy.
    Justin F Creeden, Jonathan Sevier, Jian-Ting Zhang, Yakov Lapitsky, F Charles Brunicardi, Ge Jin, John Nemunaitis, Jing-Yuan Liu, Andrea Kalinoski, Donald Rao, Shi-He Liu.
      Exosomes continue to attract interest as a promising nanocarrier drug delivery technology. They are naturally derived nanoscale extracellular vesicles with innate properties well suited to shuttle proteins, lipids, and nucleic acids between cells. Nonetheless, their clinical utility is currently limited by several major challenges, such as their inability to target tumor cells and a high proportion of clearance by the mononuclear phagocyte system (MPS) of the liver and spleen. To overcome these limitations, we developed "Smart Exosomes" that co-display RGD and CD47p110-130 through CD9 engineering (ExoSmart). The resultant ExoSmart demonstrates enhanced binding capacity to αvβ3 on pancreatic ductal adenocarcinoma (PDAC) cells, resulting in amplified cellular uptake in in vitro and in vivo models and increased chemotherapeutic efficacies. Simultaneously, ExoSmart significantly reduced liver and spleen clearance of exosomes by inhibiting macrophage phagocytosis via CD47p110-130 interaction with signal regulatory proteins (SIRPα) on macrophages. These studies demonstrate that an engineered exosome drug delivery system increases PDAC therapeutic efficacy by enhancing active PDAC targeting and prolonging circulation times, and their findings hold tremendous translational potential for cancer therapy while providing a concrete foundation for future work utilizing novel peptide-engineered exosome strategies.
    Keywords:  Bioengineering; CD47; CD9; Drug delivery; Exosomes; Gemcitabine; Paclitaxel; Pancreatic cancer; RGD
    DOI:  https://doi.org/10.1016/j.jconrel.2024.02.037
  9. Oncogene. 2024 Mar 07.
    Exosomal lncRNA XIST promotes perineural invasion of pancreatic cancer cells via miR-211-5p/GDNF.
    Ke Cheng, Jinjin Pan, Qinlong Liu, Yuke Ji, Liang Liu, Xiangqian Guo, Qiang Wang, Shao Li, Jinyue Sun, Miaomiao Gong, Ying Zhang, Yuhui Yuan.
      Perineural invasion (PNI) is an essential form of tumor metastasis in multiple malignant cancers, such as pancreatic cancer, prostate cancer, and head and neck cancer. Growing evidence has revealed that pancreatic cancer recurrence and neuropathic pain positively correlate with PNI. Therefore, targeting PNI is a proper strategy for pancreatic cancer treatment. Exosomal lncRNA derived from pancreatic cancer cells is an essential component of the tumor microenvironment. However, whether exosomal lncXIST derived from pancreatic cancer cells can promote PNI and its exact mechanism remains to be elucidated. We show that lncXIST mediates nerve-tumor crosstalk via exosomal delivery. Our data reveal that exosomal lncXIST derived from pancreatic cancer cells is delivered to neural cells and promotes their release of glial-cell-line-derived neurotrophic factor (GDNF), essential in facilitating the PNI of pancreatic cancer. Mechanistically, microRNA-211-5p negatively regulates GDNF, and lncXIST serves as a miR-211-5p sponge. The function of exosomes in the dynamic interplay between nerves and cancer is confirmed in both in vivo and in vitro PNI models. Therefore, targeting pancreatic cancer cell-derived exosomal lncXIST may provide clues for a promising approach for developing a new strategy to combat PNI of pancreatic cancer.
    DOI:  https://doi.org/10.1038/s41388-024-02994-6
  10. Int J Nanomedicine. 2024 ;19 1923-1949
    Exosomes as Powerful Biomarkers in Cancer: Recent Advances in Isolation and Detection Techniques.
    Qiongdan Zhang, Huizhen Wang, Qingyi Liu, Ni Zeng, Gang Fu, Yixing Qiu, Yupei Yang, Hanwen Yuan, Wei Wang, Bin Li.
      Exosomes, small extracellular vesicles derived from cells, are known to carry important bioactive molecules such as proteins, nucleic acids, and lipids. These bioactive components play crucial roles in cell signaling, immune response, and tumor metastasis, making exosomes potential diagnostic biomarkers for various diseases. However, current methods for detecting tumor exosomes face scientific challenges including low sensitivity, poor specificity, complicated procedures, and high costs. It is essential to surmount these obstacles to enhance the precision and dependability of diagnostics that rely on exosomes. Merging DNA signal amplification techniques with the signal boosting capabilities of nanomaterials presents an encouraging strategy to overcome these constraints and improve exosome detection. This article highlights the use of DNA signal amplification technology and nanomaterials' signal enhancement effect to improve the detection of exosomes. This review seeks to offer valuable perspectives for the enhancement of amplification methods applied in practical cancer diagnosis and prognosis by providing an overview of how these novel technologies are utilized in exosome-based diagnostic procedures.
    Keywords:  DNA signal amplification; exosomes; nanomaterials; tumor
    DOI:  https://doi.org/10.2147/IJN.S453545
  11. Mol Cancer. 2024 Mar 08. 23(1): 49
    Exosome circATP8A1 induces macrophage M2 polarization by regulating the miR-1-3p/STAT6 axis to promote gastric cancer progression.
    Cuncan Deng, Mingyu Huo, Hongwu Chu, Xiaomei Zhuang, Guofei Deng, Wenchao Li, Hongfa Wei, Leli Zeng, Yulong He, Huashan Liu, Jia Li, Changhua Zhang, Hengxing Chen.
      Circular RNAs (circRNAs) play important roles in gastric cancer progression but the regulatory role of circRNAs in controlling macrophage function remains elusive. Exosomes serve as cargo for circRNAs and play a crucial role as mediators in facilitating communication between cancer cells and the tumor microenvironment. In this study, we found that circATP8A1, a previously unreported circular RNA, is highly expressed in both gastric cancer tissues and exosomes derived from plasma. Increased circATP8A1 was associated with advanced TNM stage and worse prognosis in patients with gastric cancer. We showed that  the circATP8A1 knockdown significantly inhibited gastric cancer proliferation and invasion in vitro and in vivo. Functionally, exosome circATP8A1 induced the M2 polarization of macrophages through the STAT6 pathway instead of the STAT3 pathway. Mechanistically, circATP8A1 was shown to activate the STAT6 pathway through competitive binding to miR-1-3p, as confirmed by Fluorescence In Situ Hybridization (FISH), RNA immunoprecipitation, RNA pulldown, and Luciferase reporter assays. The reversal of circATP8A1-induced STAT6 pathway activation and macrophage polarization was observed upon blocking miR-1-3p. Macrophages treated with exosomes from gastric cancer cells overexpressing circATP8A1 were able to promote gastric cancer migration, while knockdown of circATP8A1 reversed these effects in vivo. In summary, exosome-derived circATP8A1 from gastric cancer cells induce macrophages M2 polarization via the circATP8A1/miR-1-3p/STAT6 axis, and tumor progression. Our results highlight circATP8A1 as a potential prognostic biomarker and therapeutic target in gastric cancer.
    Keywords:  Exosomes; Gastric cancer; M2 polarization; Macrophages; STAT6
    DOI:  https://doi.org/10.1186/s12943-024-01966-4
  12. J Extracell Vesicles. 2024 Mar;13(3): e12419
    Extracellular vesicles as a promising source of lipid biomarkers for breast cancer detection in blood plasma.
    Erika Dorado, Maria Luisa Doria, Anika Nagelkerke, James S McKenzie, Stefania Maneta-Stavrakaki, Thomas E Whittaker, Jeremy K Nicholson, Raoul Charles Coombes, Molly M Stevens, Zoltan Takats.
      Extracellular vesicles (EVs), including exosomes and microvesicles, mediate intercellular communication in cancer, from development to metastasis. EV-based liquid biopsy is a promising strategy for cancer diagnosis as EVs can be found in cancer patients' body fluids. In this study, the lipid composition of breast cancer-derived EVs was studied as well as the potential of blood plasma EVs for the identification of lipid biomarkers for breast cancer detection. Initially, an untargeted lipidomic analysis was carried out for a panel of cancerous and non-cancerous mammary epithelial cells and their secreted EVs. We found that breast cancer-derived EVs are enriched in sphingolipids and glycerophospholipids compared to their parental cells. The initial in vitro study showed that EVs and their parental cells can be correctly classified (100% accuracy) between cancerous and non-cancerous, as well as into their respective breast cancer subtypes, based on their lipid composition. Subsequently, an untargeted lipidomic analysis was carried out for blood plasma EVs from women diagnosed with breast cancer (primary or progressive metastatic breast cancer) as well as healthy women. Correspondingly, when blood plasma EVs were analysed, breast cancer patients and healthy women were correctly classified with an overall accuracy of 93.1%, based on the EVs' lipid composition. Similarly, the analysis of patients with primary breast cancer and healthy women showed an overall accuracy of 95% for their correct classification. Furthermore, primary and metastatic breast cancers were correctly classified with an overall accuracy of 89.5%. This reveals that the blood plasma EVs' lipids may be a promising source of biomarkers for detection of breast cancer. Additionally, this study demonstrates the usefulness of untargeted lipidomics in the study of EV lipid composition and EV-associated biomarker discovery studies. This is a proof-of-concept study and a starting point for further analysis on the identification of EV-based biomarkers for breast cancer.
    Keywords:  breast cancer; extracellular vesicles; lipidomics; liquid biopsy; mass spectrometry
    DOI:  https://doi.org/10.1002/jev2.12419
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