bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2023‒03‒19
seven papers selected by
Muhammad Rizwan
COMSATS University
  1. Exosomal miR-93-5p as an important driver of bladder cancer progression.
  2. Exosomal circular RNAs: New player in breast cancer progression and therapeutic targets.
  3. Tumor-associated macrophages-derived exo-let-7a promotes osteosarcoma metastasis via targeting C15orf41 in osteosarcoma.
  4. STIM1-regulated exosomal EBV-LMP1 empowers endothelial cells with an aggressive phenotype by activating the Akt/ERK pathway in nasopharyngeal carcinoma.
  5. Engineered exosomes from different sources for cancer-targeted therapy.
  6. Hypoxic nasopharyngeal carcinoma-derived exosomal miR-455 increases vascular permeability by targeting ZO-1 to promote metastasis.
  7. Exosomal PD‑L1 promotes the formation of an immunosuppressive microenvironment in gastric diffuse large B‑cell lymphoma.
  1. Transl Androl Urol. 2023 Feb 28. 12(2): 286-299
    Exosomal miR-93-5p as an important driver of bladder cancer progression.
    Feng Yuan, Xiao-Yu Yin, Yu Huang, Xiao-Wei Cai, Lu Jin, Guang-Cheng Dai, Ya-Cheng Zang, Yi Sun, Xiao-Long Liu, Bo-Xin Xue.
      Background: Tumor-derived exosomes are involved in the process of tumor metastasis and angiogenesis. MicroRNAs (miRNAs) are the most widely investigated factors in exosomes. Therefore, we hope to find a new therapeutic target in bladder cancer (BLCA), which has high incidence rate and mortality.Methods: Exosomal microRNA(miR)-93-5p expression level, downstream target molecules, and biological functions were examined with bioinformatics technology. Exosomes were extracted by sequential differential centrifugation and verified by transmission electron microscopy. The exosomal miR-93-5p on cell proliferation, invasion, and angiogenesis abilities in 5637 and T24 cells was determined by Cell Counting Kit 8 (CCK-8), colony-forming assay, Transwell assay, and vascular ring formation assay. A mouse xenograft model with intratumor injection was adopted to evaluate the correlation between BLCA-derived exosomes and tumor growth in vivo.
    Results: The results revealed that exosomes play an important role in the biological progression of BLCA, with miR-93-5p being a particularly important molecule. Compared to normal cells, more malignant cells release more exosomal miR-93-5p, and tumor-derived exosomal miR-93-5p could significantly promote cell proliferation, invasion, and angiogenesis in vitro and in vivo. We identified phosphatase and tensin homolog (PTEN) as the most significant target of miR-93-5p in BLCA and human umbilical vein endothelial cells.
    Conclusions: Our study successfully revealed the biological role and mechanism of BLCA-derived exosomes in tumor progression. Target at tumor exosomes and exosomal miR-93-5p may be an effective treatment in BLCA.
    Keywords:  Exosomes; angiogenesis; bladder cancer; miR-93-5p; tumor microenvironment
    DOI:  https://doi.org/10.21037/tau-22-872
  2. Front Genet. 2023 ;14 1126944
    Exosomal circular RNAs: New player in breast cancer progression and therapeutic targets.
    Bashdar Mahmud Hussen, Sayran Mohamadtahr, Snur Rasool Abdullah, Hazha Jamal Hidayat, Mohammad Fatih Rasul, Goran Sedeeq Hama Faraj, Soudeh Ghafouri-Fard, Mohammad Taheri, Maryam Khayamzadeh, Elena Jamali.
      Breast cancer is the most prevalent type of malignancy among women. Exosomes are extracellular vesicles of cell membrane origin that are released via exocytosis. Their cargo contains lipids, proteins, DNA, and different forms of RNA, including circular RNAs. Circular RNAs are new class of non-coding RNAs with a closed-loop shape involved in several types of cancer, including breast cancer. Exosomes contained a lot of circRNAs which are called exosomal circRNAs. By interfering with several biological pathways, exosomal circRNAs can have either a proliferative or suppressive role in cancer. The involvement of exosomal circRNAs in breast cancer has been studied with consideration to tumor development and progression as well as its effects on therapeutic resistance. However, its exact mechanism is still unclear, and there have not been available clinical implications of exo-circRNAs in breast cancer. Here, we highlight the role of exosomal circRNAs in breast cancer progression and to highlight the most recent development and potential of circRNAas therapeutic targets and diagnostics for breast cancer.
    Keywords:  breast cancer (BC); circular RNA (circRNA); exosomal circRNA (exo-circRNA); exosome; therapeutic target
    DOI:  https://doi.org/10.3389/fgene.2023.1126944
  3. Environ Toxicol. 2023 Mar 15.
    Tumor-associated macrophages-derived exo-let-7a promotes osteosarcoma metastasis via targeting C15orf41 in osteosarcoma.
    Chen-Fei Yan, Jun Xia, Wang-Si Qun, Wei-Yi Bing, Wu-Jian Guo, Huang-Gang Yong, Chen-Jie, Shi-Jing Sheng, Zhao-Guang Lei, Huang-Xin.
      BACKGROUND: Osteosarcoma (OS) immune environment is complexed and the immune factors-related to OS progression need to be explored. Tumor-associated macrophages (TAMs) are regarded as immune suppressive and tumor-promoting cells. However, the underlying mechanisms through which TAMs function are still fragmentary. Here, we aim to explore the underlying mechanisms by which TAMs regulate OS progression.METHODS: TAMs from OS tissues were isolated by flow cytometry. Exosomes derived from TAMs were separated using ultracentrifugation and western blotting. Transmission electron microscopy (TEM), and flow cytometry were constructed to characterize TAMs-derived exosomes. Additionally, the differential MicroRNAs (miRNAs) and genes were detected through RNA sequencing, and further validated using real-time PCR (RT-PCR). OS cell metastasis ability was assessed using transwell invasion and scratch wound healing assays. MiRNAs mimic and lentiviral vectors were utilized to explore the effects on OS progression.
    RESULTS: Exosome secreted by TAMs accelerated the OS metastasis. Let-7a level was upregulated in TAMs derived exosomes, which downregulated C15orf41 by targeting 3'-untranslated region (UTR). Furthermore, overexpressing let-7a enhanced invasion and migration by blocking the transcription of C15orf41. In consistent, up-regulating let-7a promoted OS progression and made the prognosis to be worse, which can be reversed by C15orf41 overexpression.
    CONCLUSION: This study highlighted the critical role of TAMs-derived exosomes in OS progression and explored the potential value of the let-7a/C15orf41 axis as an indicator or target for OS.
    Keywords:  C15orf41; TAMs; exosomes; let-7a; metastasis; osteosarcoma
    DOI:  https://doi.org/10.1002/tox.23766
  4. Cell Oncol (Dordr). 2023 Mar 14.
    STIM1-regulated exosomal EBV-LMP1 empowers endothelial cells with an aggressive phenotype by activating the Akt/ERK pathway in nasopharyngeal carcinoma.
    Yayan Deng, Xue Liu, Yujuan Huang, Jiaxiang Ye, Qian He, Yue Luo, Yong Chen, Qiuyun Li, Yan Lin, Rong Liang, Yongqiang Li, Jiazhang Wei, Jinyan Zhang.
      BACKGROUND: Stromal interaction molecule 1 (STIM1)-mediated Ca2+ signaling regulates tumor angiogenesis in nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-related human malignancy. However, the mechanism by which STIM1 modulates endothelial functional phenotypes contributing to tumor angiogenesis remains elusive.METHODS: NPC cell-derived exosomes were isolated via differential centrifugation and observed using transmission electron microscopy. Exosome particle sizes were assessed by nanoparticle tracking analysis (NTA). Uptake of exosomes by recipient ECs was detected by fluorescent labeling of the exosomes with PKH26. Tumor angiogenesis-associated profiles were characterized by determining cell proliferation, migration, tubulogenesis and permeability in human umbilical vein endothelial cells (HUVECs). Activation of the Akt/ERK pathway was assessed by detecting the phosphorylation levels using Western blotting. A chick embryo chorioallantoic membrane (CAM) xenograft model was employed to study tumor-associated neovascularization in vivo.
    RESULTS: We found that NPC cell-derived exosomes harboring EBV-encoded latent membrane protein 1 (LMP1) promoted proliferation, migration, tubulogenesis and permeability by activating the Akt/ERK pathway in ECs. STIM1 silencing reduced LMP1 enrichment in NPC cell-derived exosomes, thereby reversing its pro-oncogenic effects in an Akt/ERK pathway-dependent manner. Furthermore, STIM1 knockdown in NPC cells blunted tumor-induced vascular network formation and inhibited intra-tumor neovascularization in the chorioallantoic membrane (CAM) xenograft model.
    CONCLUSION: STIM1 regulates tumor angiogenesis by controlling exosomal EBV-LMP1 delivery to ECs in the NPC tumor microenvironment. Blocking exosome-mediated cell-to-cell horizontal transfer of EBV-associated oncogenic signaling molecules may be an effective therapeutic strategy for NPC.
    Keywords:  Angiogenesis; Latent membrane protein 1; Nasopharyngeal carcinoma; Stromal interaction molecule 1; Tumor-derived exosomes
    DOI:  https://doi.org/10.1007/s13402-023-00790-0
  5. Signal Transduct Target Ther. 2023 Mar 15. 8(1): 124
    Engineered exosomes from different sources for cancer-targeted therapy.
    Menghui Zhang, Shengyun Hu, Lin Liu, Pengyuan Dang, Yang Liu, Zhenqiang Sun, Bingbing Qiao, Chengzeng Wang.
      Exosome is a subgroup of extracellular vesicles, which has been serving as an efficient therapeutic tool for various diseases. Engineered exosomes are the sort of exosomes modified with surface decoration and internal therapeutic molecules. After appropriate modification, engineered exosomes are able to deliver antitumor drugs to tumor sites efficiently and precisely with fewer treatment-related adverse effects. However, there still exist many challenges for the clinical translation of engineered exosomes. For instance, what sources and modification strategies could endow exosomes with the most efficient antitumor activity is still poorly understood. Additionally, how to choose appropriately engineered exosomes in different antitumor therapies is another unresolved problem. In this review, we summarized the characteristics of engineered exosomes, especially the spatial and temporal properties. Additionally, we concluded the recent advances in engineered exosomes in the cancer fields, including the sources, isolation technologies, modification strategies, and labeling and imaging methods of engineered exosomes. Furthermore, the applications of engineered exosomes in different antitumor therapies were summarized, such as photodynamic therapy, gene therapy, and immunotherapy. Consequently, the above provides the cancer researchers in this community with the latest ideas on engineered exosome modification and new direction of new drug development, which is prospective to accelerate the clinical translation of engineered exosomes for cancer-targeted therapy.
    DOI:  https://doi.org/10.1038/s41392-023-01382-y
  6. Mol Carcinog. 2023 Mar 17.
    Hypoxic nasopharyngeal carcinoma-derived exosomal miR-455 increases vascular permeability by targeting ZO-1 to promote metastasis.
    Lixiao Xie, Kaiwen Zhang, Bo You, Haimeng Yin, Panpan Zhang, Ying Shan, Zhifeng Gu, Qicheng Zhang.
      Nasopharyngeal carcinoma (NPC), the most frequent reason for treatment failure in head and neck tumors, has the greatest incidence of distant metastases. Increased vascular permeability facilitates metastasis. Exosomal microRNAs (miRNAs) have been implicated in the development of the premetastatic niche and are emerging as prospective biomarkers in cancer patients. We discovered that a higher level of miR-455 was connected to a larger propensity for NPC metastasis based on deep sequencing and RT-qPCR. We found that hypoxia promoted NPC exosomes release and increased miR-455 expression in a way that was hypoxia-inducible factor 1-alpha (HIF-1α) dependent. Exosomes from NPC cells with high levels of miR-455 were found to specifically target zonula occludens 1 (ZO-1), increasing the permeability of endothelial monolayers in vitro vascular permeability and transendothelial invasion experiments. Additional in vivo studies showed that zebrafish with sustained miR-455-overexpressing NPC cell xenografts displayed increased tumor cell mass throughout the body. In vivo, zebrafish vascular tight junction integrity was disrupted by exosomes produced by NPC cells with elevated miR-455 expression. Mice-bearing xenografts further supported the finding that exosomes containing miR-455 might reduce ZO-1 expression in addition to promote NPC cell growth. These findings suggest that in a hypoxic microenvironment, exosomal miR-455 released by NPC cells enhances vascular permeability and promotes metastasis by targeting ZO-1. The HIF-1α-miR-455-ZO-1 signaling pathway may be a promising predictor and potential therapeutic target for NPC with metastasis.
    Keywords:  exosomes; metastasis; miR-455; nasopharyngeal carcinoma; vascular permeability
    DOI:  https://doi.org/10.1002/mc.23525
  7. Oncol Rep. 2023 May;pii: 88. [Epub ahead of print]49(5):
    Exosomal PD‑L1 promotes the formation of an immunosuppressive microenvironment in gastric diffuse large B‑cell lymphoma.
    Hui Zeng, Jinfeng Wang, Biaoming Xu, Hongyu Deng, Mingjing Peng, Rilin Deng, Song Shang, Qi Hu, Junjun Li, Jinguan Lin, Haizhen Zhu, Yajun Li, Chaohui Zuo.
      Gastric diffuse large B‑cell lymphoma (GDLBCL) is a common disease with an increasing incidence. However, the regulatory effect of exosomal programmed death‑ligand 1 (PD‑L1) on the immune microenvironment in GDLBCL is unclear. In the present study, the protein expression levels of exosomal PD‑L1 in the supernatants of cultured diffuse large B‑cell lymphoma (DLBCL) cells and the plasma of patients with GDLBCL was assessed using immunoblotting. Exosomes derived from DLBCL cells were cocultured with T lymphocytes or injected into tumor xenograft mice by tail vein injection. The relationship between the protein expression level of exosomal PD‑L1 in the plasma and the clinical characteristics and immune microenvironmental parameters of GDLBCL was evaluated using immunoblotting and immunohistochemistry. High levels of exosomal PD‑L1 were found in the supernatants of cultured DLBCL cells. Exosomes with high levels of PD‑L1 promoted growth of tumors formed by DLBCL cells in vivo and inhibited the proliferation of T lymphocytes. Notably, the protein expression level of PD‑L1 in plasma exosomes derived from GDLBCL patients was significantly higher than that of healthy individuals. High levels of PD‑L1 in plasma exosomes were significantly associated with international prognostic index score, pathological type and advanced Lugano stage, which might lead to the poor prognosis of GDLBCL. Moreover, a high level of PD‑L1 in plasma exosomes was significantly associated with an immunosuppressive microenvironment in GDLBCL. Therefore, the results of the present study indicated that exosomal PD‑L1 inhibited the proliferation of T lymphocytes and promoted the formation of an immunosuppressive microenvironment in GDLBCL. High expression of exosomal PD‑L1 may suggest a poor prognosis of GDLBCL, and exosomal PD‑L1 in plasma may be a new diagnostic indicator for GDLBCL.
    Keywords:  PD‑L1; exosomes; gastric diffuse large B‑cell lymphoma; immune microenvironment; immunosuppression
    DOI:  https://doi.org/10.3892/or.2023.8525
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