bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2024–11–17
nine papers selected by
Muhammad Rizwan, COMSATS University
  1. Known and unknown: Exosome secretion in tumor microenvironment needs more exploration.
  2. Exosomal AHSG in ovarian cancer ascites inhibits malignant progression of ovarian cancer by p53/FAK/Src signaling.
  3. Extracellular vesicles in hepatocellular carcinoma: unraveling immunological mechanisms for enhanced diagnosis and overcoming drug resistance.
  4. Exosomal integrins in tumor progression, treatment and clinical prediction (Review).
  5. Pancreatic cancer-derived exosomal miR-510 promotes macrophage M2 polarization and facilitates cancer cell aggressive phenotypes.
  6. Colon Cancer-Derived Exosomal LncRNA-XIST Promotes M2-like Macrophage Polarization by Regulating PDGFRA.
  7. Exosomal PSM-E inhibits macrophage M2 polarization to suppress prostate cancer metastasis through the RACK1 signaling axis.
  8. Engineered Macrophage Exosomes Deliver Drug-Targeted Therapy for Breast Cancer.
  9. Unlocking the Secrets of Extracellular Vesicles: Orchestrating Tumor Microenvironment Dynamics in Metastasis, Drug Resistance, and Immune Evasion.
  1. Genes Dis. 2025 Jan;12(1): 101175
    Known and unknown: Exosome secretion in tumor microenvironment needs more exploration.
    Mengxiang Huang, Jie Ji, Xuebing Xu, Dandan Jin, Tong Wu, Renjie Lin, Yuxuan Huang, Jiawen Qian, Zhonghua Tan, Feng Jiang, Xiaogang Hu, Weisong Xu, Mingbing Xiao.
      Exosomes, extracellular vesicles originating from endosomes, were discovered in the late 1980s and their function in intercellular communication has since garnered considerable interest. Exosomes are lipid bilayer-coated vesicles that range in size from 30 to 150 nm and appear as sacs under the electron microscope. Exosome secretion is crucial for cell-to-cell contact in both normal physiology and the development and spread of tumors. Furthermore, cancer cells can secrete more exosomes than normal cells. Scientists believe that intercellular communication in the complex tissue environment of the human body is an important reason for cancer cell invasion and metastasis. For example, some particles containing regulatory molecules are secreted in the tumor microenvironment, including exosomes. Then the contents of exosomes can be released by donor cells into the environment and interact with recipient cells to promote the migration and invasion of tumor cells. Therefore, in this review, we summarized the biogenesis of exosome, as well as exosome cargo and related roles. More importantly, this review introduces and discusses the factors that have been reported to affect exosome secretion in tumors and highlights the important role of exosomes in tumors.
    Keywords:  Exosome cargo; Exosome secretion; Intercellular communication; Tumor; Tumor microenvironment
    DOI:  https://doi.org/10.1016/j.gendis.2023.101175
  2. Transl Cancer Res. 2024 Oct 31. 13(10): 5365-5380
    Exosomal AHSG in ovarian cancer ascites inhibits malignant progression of ovarian cancer by p53/FAK/Src signaling.
    Guangyan Xie, Yongli Zhang, Jiachen Ma, Xiaoli Guo, Jiahao Xu, Linna Chen, Jingbo Zhang, Yanyu Li, Bei Zhang, Xueyan Zhou.
       Background: The primary cause of mortality in patients with ovarian cancer (OC) is tumor metastasis. A comprehensive understanding of the mechanisms underlying metastasis in OC is essential for accurate prognosis prediction and the development of targeted therapeutic agents. Our findings indicate that alpha-2 Heremans Schmid glycoprotein (AHSG) is downregulated in OC exosomes. Consequently, the objective of this study was to identify novel prognostic markers and potential therapeutic targets for OC.
    Methods: Exosomes derived from OC cells and patient ascites were purified and applied to OC cells to assess their migratory ability using wound-healing and transwell assays. AHSG expression was enhanced by overexpressing lentivirus, and the resulting exosomes were isolated and co-cultured with OC cells to verify their effect on the migration ability of OC.
    Results: Exosomes in ovarian malignant ascites have been demonstrated to promote OC metastasis. However, our findings indicate that AHSG is down-regulated in OC tissues and ascites exosomes. Furthermore, overexpression of AHSG in OC cells has been shown to markedly decrease their migratory ability, as well as reduce the migratory ability of cancer cells after co-culture of its exosomes with cancer cells.
    Conclusions: The low expression of AHSG in exosomes derived from OC tissues and ascites is associated with metastatic progression in OC patients. Additionally, cancer-derived AHSG can be transported to OC cells via exosomes, where it inhibits OC migration in vitro and in vivo by regulating the p53/FAK/Src signaling pathway. The present study demonstrated that AHSG, derived from cancer cells, exerts a negative regulatory effect on OC cell motility, migration, and metastasis. These findings suggest that AHSG is a potential candidate for OC treatment.
    Keywords:  Alpha-2 Heremans Schmid glycoprotein (AHSG); ascites; exosomes; migration; ovarian cancer (OC)
    DOI:  https://doi.org/10.21037/tcr-24-789
  3. Front Immunol. 2024 ;15 1485628
    Extracellular vesicles in hepatocellular carcinoma: unraveling immunological mechanisms for enhanced diagnosis and overcoming drug resistance.
    Lanqian Su, Yuxin Yue, Yalan Yan, Jianming Sun, Lanxin Meng, Jiaan Lu, Lanyue Zhang, Jie Liu, Hao Chi, Sinian Liu, Zhongqiu Yang, Xiaowei Tang.
      Current research is focused on utilizing EVs as a biopsy tool to improve the diagnostic accuracy of HCC, reduce surgical risk, and explore their potential in modulating drug resistance and advancing immunotherapeutic strategies. Extracellular vesicles (EVs) have been increasingly recognized as important non-invasive biomarkers in hepatocellular carcinoma (HCC) due to the presence of a variety of biomolecules within them, such as proteins and RNAs, etc. EVs play a key role in the early detection, diagnosis, treatment, and prognostic monitoring of HCC. These vesicles influence the development of HCC and therapeutic response in a variety of ways, including influencing the tumor microenvironment, modulating drug resistance, and participating in immune regulatory mechanisms. In addition, specific molecules such as miRNAs and specific proteins in EVs are regarded as potential markers for monitoring treatment response and recurrence of HCC, which have certain research space and development prospects. In this paper, we summarize the aspects of EVs as HCC diagnostic and drug resistance markers, and also discuss the questions that may be faced in the development of EVs as markers.
    Keywords:  diagnosis; drug resistance; extracellular vesicles; hepatocellular carcinoma; tumor marker
    DOI:  https://doi.org/10.3389/fimmu.2024.1485628
  4. Int J Oncol. 2024 Dec;pii: 118. [Epub ahead of print]65(6):
    Exosomal integrins in tumor progression, treatment and clinical prediction (Review).
    Yu-Qing Shen, Lei Sun, Shi-Ming Wang, Xian-Yu Zheng, Rui Xu.
      Integrins are a large family of cell adhesion molecules involved in tumor cell differentiation, migration, proliferation and neovascularization. Tumor cell‑derived exosomes carry a large number of integrins, which are closely associated with tumor progression. As crucial mediators of intercellular communication, exosomal integrins have gained attention in the field of cancer biology. The present review examined the regulatory mechanisms of exosomal integrins in tumor cell proliferation, migration and invasion, and emphasized their notable roles in tumor initiation and progression. The potential of exosomal integrins as drug delivery systems in cancer treatment was explored. Additionally, the potential of exosomal integrins in clinical tumor prediction was considered, while summarizing their applications in diagnosis, prognosis assessment and treatment response prediction. Thus, the present review aimed to provide guidance and insights for future basic research and the clinical translation of exosomal integrins. The study of exosomal integrins is poised to offer new perspectives and methods for precise cancer treatment and clinical prediction.
    Keywords:  biomarkers; exosome; integrin; treatment; tumor progression
    DOI:  https://doi.org/10.3892/ijo.2024.5706
  5. Hum Cell. 2024 Nov 12. 38(1): 17
    Pancreatic cancer-derived exosomal miR-510 promotes macrophage M2 polarization and facilitates cancer cell aggressive phenotypes.
    Tao Wang, Lin Ye, Yingjie Zhou, Xionghan Zhang, Renjian Li, Yi Zhou, Jun Weng, Qingrong Mo, Yaqun Yu.
      Extensive tumor microenvironment (TME) and tumor-associated macrophages (TAMs) contribute to the initiation and progression of pancreatic cancer (PC). Cancer cell-derived exosomal miRNAs that stimulate macrophage M2 polarization might play an important role in the process. In the current study, we observed significant upregulation of miR-510 in PC cell lines in comparison to normal HPDE cell line, with PANC-1 exhibiting the highest and MIA PaCa-2 the lowest miR-510 levels. Functional assays demonstrated that miR-510 overexpression enhanced, while its inhibition reduced, PC cell viability, migration, invasion, and EMT. In vivo, miR-510 mimics promoted tumor growth and macrophage M2 polarization, whereas miR-510 inhibition had the opposite effect. Exosomes from PANC-1 and MIA PaCa-2 cells, characterized by nanoparticle tracking analysis and TEM, contained significantly higher miR-510 levels than those from HPDE cells. Macrophages incubated with conditioned media from these PC cells showed increased M2 polarization markers, a process inhibited by the exosome inhibitor GW4869. The delivery of miR-510 via PC cell-derived exosomes facilitated macrophage M2 polarization and regulated the STAT signaling pathway, suggesting that exosomal miR-510 plays a crucial role in the tumor microenvironment of PC by modulating macrophage M2 polarization.
    Keywords:  Pancreatic cancer (PC); miR-510; macrophage M2 polarization; STAT signaling
    DOI:  https://doi.org/10.1007/s13577-024-01144-0
  6. Int J Mol Sci. 2024 Oct 24. pii: 11433. [Epub ahead of print]25(21):
    Colon Cancer-Derived Exosomal LncRNA-XIST Promotes M2-like Macrophage Polarization by Regulating PDGFRA.
    Beibei Gao, Li Wang, Ting Wen, Xiaoge Xie, Xiaoyi Rui, Qiaoyi Chen.
      Colon cancer ranks second in overall cancer-related deaths and poses a serious risk to human life and health. In recent years, exosomes are believed to play an important and significant role in cancer, especially tumor-derived exosomes (TDEs). Previous studies have highlighted the pivotal role of exosomes in tumor development, owing to their ability to mediate communication between tumor cells and macrophages, induce macrophage M2 polarization, and facilitate the progression of tumorigenesis. In this study, we revealed that colon cancer-derived exosomes promoted M2-like macrophage polarization. Moreover, exosome-induced M2-like macrophages, in turn, promoted the proliferation, migration, and invasion abilities of colon cancer cells. Specifically, CT26- and HCT116-derived exosomes led to the activation of AKT, ERK, and STAT3/6 signaling pathways in THP-1(Mφ) cells. Furthermore, our findings showed that colon cancer-derived exosomes secreted lncXIST to sponge miR-17-5p, which, in turn, promoted the expression of PDGFRA, a common gene found in all three signaling pathways, to facilitate M2-like macrophage polarization. Dual-luciferase reporter assays confirmed the binding relationship between lncXIST and miR-17-5p, as well as miR-17-5p and PDGFRA. Collectively, our results highlight the novel role of lncXIST in facilitating macrophage polarization by sponging miR-17-5p and regulating PDGFRA expression.
    Keywords:  LncXIST; PDGFRA; exosomes; macrophage; miR-17-5p; polarization
    DOI:  https://doi.org/10.3390/ijms252111433
  7. Biomark Res. 2024 Nov 14. 12(1): 138
    Exosomal PSM-E inhibits macrophage M2 polarization to suppress prostate cancer metastasis through the RACK1 signaling axis.
    Xingliang Qin, Rouxi Niu, Yongyao Tan, Yuxin Huang, Weishu Ren, Weiwei Zhou, Huiquan Wu, Junlong Zhang, Mingze Xu, Xiang Zhou, Hongyu Guan, Xun Zhu, Yu Chen, Kaiyuan Cao.
       BACKGROUND: It is well-established that understanding the mechanism of prostate cancer (PCa)-associated metastasis is paramount for improving its prognosis. Metastasis is known to involve the communication between tumor-associated macrophages (TAMs) and tumor cells. Exosomes are crucial in mediating this intercellular communication within the tumor microenvironment. Nonetheless, the role of exosomal proteins in PCa metastasis is not yet fully understood. Here, we investigated the mechanisms of prostate cancer-derived exosomal PSM-E on regulating macrophage M2 polarization to suppress tumor invasion and metastasis.
    METHODS: PSM-E levels in exosomes were detected by transmission electron microscopy and Western blotting analysis. The diagnostic value of urine-derived exosomal PSM-E in PCa were evaluated by LC-MS/MS, correlation analysis, and ROC curves analysis. The mechanisms underlying the inhibitory effect of exosomal PSM-E on the M2 polarization of macrophages was investigated by co-IP, IHC staining, and PCa tumorigenesis model, etc. RESULTS: We revealed that exosomal PSM-E is upregulated in exosomes derived from the serum and urine of PCa patients. Clinically, an elevated exosomal PSM-E expression in urine is significantly correlated with an advanced pathological tumor stage and a high Gleason score. Our research also revealed that exosomal PSM-E inhibits prostate cancer cell proliferation, invasion, and metastasis by suppressing macrophage polarization in vitro and in vivo. Furthermore, we provided compelling evidence that exosomal PSM-E inhibits M2 polarization of macrophages by recruiting RACK1 and suppressing the FAK and ERK signaling pathways, consequently suppressing PCa invasion and metastasis. Furthermore, we found that the protease-associated domain of PSM-E and the fourth tryptophan-aspartate repeat of RACK1 are crucial for the interaction between PSM-E and RACK1.
    CONCLUSIONS: Notably, exosomes carrying PSM-E from PCa urine could potentially serve as a biomarker for PCa, and targeting exosomal PSM-E may represent a strategy for preventing tumor progression in this patient population.
    Keywords:  Exosome; Macrophage polarization; PSM-E; Prostate cancer
    DOI:  https://doi.org/10.1186/s40364-024-00685-8
  8. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2024 Nov-Dec;16(6):16(6): e2012
    Engineered Macrophage Exosomes Deliver Drug-Targeted Therapy for Breast Cancer.
    Mingrui Feng, Lifang Zhang, Zhuoling Zou, Mengying Xie, Jianbo Zhang, Jiayang Wang, Keqin Wang, Jun Zhu, Lixia Xiong.
      Breast cancer is a highly widespread form of malignant tumor characterized by a high rate of recurrence and mortality; it primarily occurs when tumor cells spread to peripheral regions of the body. Macrophages have a significant impact on the proliferation and metastasis of breast cancer. The exosomes generated by these cells exhibit an extensive spectrum of capabilities in suppressing the spread of cancer cells. These feature very specific targeting properties for breast cancer cells and inhibit the proliferation of cancer cells by altering the immune milieu within the tumor. This study investigates methods for developing macrophage-derived exosomes, such as using protein-coupled exosome membranes to protect delivery contents, creating multifunctional biomimetic particles, and utilizing ultrasonic fusion to protect delivery contents. Furthermore, this paper addresses recent advances in producing macrophage exosomes from organic and inorganic materials. In general, targeted treatment for breast cancer could benefit greatly from creating drug delivery systems mediated by macrophage exosomes.
    Keywords:  breast cancer; drug delivery systems; macrophage exosome
    DOI:  https://doi.org/10.1002/wnan.2012
  9. J Cancer. 2024 ;15(19): 6383-6415
    Unlocking the Secrets of Extracellular Vesicles: Orchestrating Tumor Microenvironment Dynamics in Metastasis, Drug Resistance, and Immune Evasion.
    Rashid Mir, Sadaf Khursheed Baba, Imadeldin Elfaki, Naseh Algehainy, Mohammad A Alanazi, Faisal H Altemani, Faris Jamal Tayeb, Jameel Barnawi, Eram Husain, Ruqaiah I Bedaiwi, Ibrahim Altedlawi Albalawi, Muhanad Alhujaily, Mohammad Muzaffar Mir, Reema Almotairi, Hanan E Alatwi, Aziz Dhaher Albalawi.
      Extracellular vehicles (EVs) are gaining increasing recognition as central contributors to the intricate landscape of the tumor microenvironment (TME). This manuscript provides an extensive examination of the multifaceted roles played by EVs in shaping the TME, with a particular emphasis on their involvement in metastasis, drug resistance, and immune evasion. Metastasis, the process by which cancer cells disseminate to distant sites, remains a formidable challenge in cancer management. EVs, encompassing exosomes and microvesicles, have emerged as critical participants in this cascade of events. They facilitate the epithelial-to-mesenchymal transition (EMT), foster pre-metastatic niche establishment, and enhance the invasive potential of cancer cells. This manuscript delves into the intricate molecular mechanisms underpinning these processes, underscoring the therapeutic potential of targeting EVs to impede metastasis. Drug resistance represents a persistent impediment to successful cancer treatment. EVs are instrumental in intrinsic and acquired drug resistance, acting as mediators of intercellular communication. They ferry molecules like miRNAs and proteins, which confer resistance to conventional chemotherapy and targeted therapies. This manuscript scrutinizes the diverse strategies employed by EVs in propagating drug resistance while also considering innovative approaches involving EV-based drug delivery systems to counteract this phenomenon. Immune evasion is a hallmark of cancer, and EVs are central in sculpting the immunosuppressive milieu of the TME. Tumor-derived EVs thwart immune responses through various mechanisms, including T cell dysfunction induction, the expansion of regulatory T cells (Tregs), and polarization of macrophages towards an immunosuppressive phenotype. In addition, the manuscript explores the diagnostic potential of EVs as biomarkers and their role as therapeutic agents in immune checkpoint blockade therapies. This manuscript provides a comprehensive overview of EV's pivotal role in mediating intricate interactions within the TME, ultimately influencing cancer progression and therapeutic outcomes. A profound understanding of EV-mediated processes in metastasis, drug resistance, and immune evasion opens up promising avenues for developing innovative therapeutic strategies and identifying valuable biomarkers in the ongoing battle against cancer.
    Keywords:  Exosomal miRNAs; Extracellular vesicles; Intercellular Communication; epithelial-to-mesenchymal transition; tumor microenvironment
    DOI:  https://doi.org/10.7150/jca.98426
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