bims-exocan Biomed News
on Exosomes roles in cancer
Issue of 2023–07–30
nine papers selected by
Muhammad Rizwan, COMSATS University
  1. The Roles of Exosomes in Ovarian Cancer Chemo-resistance.
  2. Pancreatic stellate cell-derived exosomal tRF-19-PNR8YPJZ promotes proliferation and mobility of pancreatic cancer through AXIN2.
  3. Roles of Extracellular Vesicles on the Progression and Metastasis of Hepatocellular Carcinoma.
  4. Applications of engineered exosomes in drugging noncoding RNAs for cancer therapy.
  5. Bleomycin loaded exosomes enhanced antitumor therapeutic efficacy and reduced toxicity.
  6. Exosomes from metastatic colon cancer cells drive the proliferation and migration of primary colon cancer through increased expression of cancer stem cell markers CD133 and DCLK1.
  7. Influence of Extracellular Vesicles on Lung Stromal Cells during Breast Cancer Metastasis.
  8. Modulation of PD‑L1 expression by standard therapy in head and neck cancer cell lines and exosomes.
  9. Recent Progress in Extracellular Vesicle-Based Carriers for Targeted Drug Delivery in Cancer Therapy.
  1. J Cancer. 2023 ;14(11): 2128-2144
    The Roles of Exosomes in Ovarian Cancer Chemo-resistance.
    Yang Liu, Xiao Li, Tianyu Zhang, Guoyan Liu.
      As common gynecological oncology, ovarian cancer has a high fatality rate and poor overall survival, mainly because of nonspecific symptoms in the early stages and chemotherapy resistance. Exosomes, nano-sized vesicles secreted by almost all types of cells, carry valuable commodities such as proteins, lipids, enzymes, mRNAs, and miRNAs between cells. They take part in remodeling the tumor microenvironment, promoting tumor angiogenesis and metastasis, and regulating immune metastasis and chemotherapy resistance in ovarian cancer. Previous studies have reported that exosomes could transfer chemotherapy resistance from drug-resistant tumor cells to sensitive ones by delivering proteins and miRNAs. Also, exosomes are involved in chemotherapy resistance by transferring multidrug-resistance-related transporters, decreasing apoptosis, promoting epithelial-to-mesenchymal transition, and changing signal transduction pathways. Furthermore, they play a significant role in early detection, chemotherapy efficacy evaluation, and treatment of ovarian cancer. Exosomes are applied as chemotherapeutic delivery vehicles and therapeutic targets to inhibit anti-tumor immune responses. In addition, exosomes can be developed for cancer immunotherapy because of their immunomodulatory potential. Therefore, the article reviews the latest research progress of exosomes in ovarian cancer to elaborate on the mechanisms of exosome-mediated chemotherapy resistance in ovarian cancer patients and provide a forecast on their clinical therapeutic potential in improving chemotherapy sensitivity.
    Keywords:  Chemotherapy resistance; Exosomes; Ovarian cancer; Therapeutic potential
    DOI:  https://doi.org/10.7150/jca.84930
  2. J Cell Mol Med. 2023 Jul 24.
    Pancreatic stellate cell-derived exosomal tRF-19-PNR8YPJZ promotes proliferation and mobility of pancreatic cancer through AXIN2.
    Wenpeng Cao, Shisi Dai, Wanyuan Ruan, Tingting Long, Zhirui Zeng, Shan Lei.
      The pancreatic stellate cells (PSCs) play an important role in the development of pancreatic cancer (PC) through mechanisms that remain unclear. Exosomes secreted from PSCs act as mediators for communication in PC. This study aimed to explore the role of PSC-derived exosomal small RNAs derived from tRNAs (tDRs) in PC cells. Exosomes from PSCs were extracted and used to detect their effects on PC cell proliferation, migration and invasion. Exosomal tDRs profiling was performed to identify PSC-derived exosomal tDRs. ISH and qRT-PCR were used to examine the tRF-19-PNR8YPJZ levels and clinical value in clinical samples. The biological function of exosomal tRF-19-PNR8YPJZ was determined using the CCK-8, clone formation, wound healing and transwell assays, subcutaneous tumour formation and lung metastatic models. The relationship between the selected exosomal tRF-19-PNR8YPJZ and AXIN2 was determined by RNA sequencing, luciferase reporter assay. PSC-derived exosomes promoted the proliferation, migration, and invasion of PC cells. Novel and abundant tDRs are found to be differentially expressed in PANC-1 cells after treatment with PSC-derived exosomes, such as tRF-19-PNR8YPJZ. PC tissue samples showed markedly higher levels of tRF-19-PNR8YPJZ than normal controls. Patients with PC exhibiting high tRF-19-PNR8YPJZ expression had a highly lymph node invasion, metastasis, perineural invasion, advanced clinical stage and poor overall survival. Exosomal tRF-19-PNR8YPJZ from PSCs targeted AXIN2 in PC cells and decreased its expression, thus activating the Wnt pathway and promoting proliferation and metastasis. Exosomal tRF-19-PNR8YPJZ from PSCs promoted proliferation and metastasis in PC cells via AXIN2.
    Keywords:  AXIN2; exosomal; metastasis; pancreatic cancer; tRF-19-PNR8YPJZ
    DOI:  https://doi.org/10.1111/jcmm.17852
  3. Cells. 2023 Jul 18. pii: 1879. [Epub ahead of print]12(14):
    Roles of Extracellular Vesicles on the Progression and Metastasis of Hepatocellular Carcinoma.
    Turner W Seay, Zucai Suo.
      Liver cancer is a global health challenge as it is the third leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is often found in liver cells, where it is associated with high morbidity and mortality rates. Recent studies have shown that extracellular vesicles (EVs) secreted by HCC cells play a critical role in HCC progression and metastasis. EVs contain proteins, nucleic acids, lipids, and metabolites as cargos. EVs derived from HCC cells can transfer oncogenic factors to surrounding cells leading to increased tumor growth, cell invasion, and angiogenesis. In this review, we summarize the roles that EVs play and the specific effects of their cargos on HCC progression and metastasis and identify potential therapeutic targets for HCC treatment.
    Keywords:  circular RNAs; enzymes; exosomes; extracellular vesicles; hepatocellular carcinoma; liver cancer; metastasis
    DOI:  https://doi.org/10.3390/cells12141879
  4. Chem Biol Drug Des. 2023 Jul 26.
    Applications of engineered exosomes in drugging noncoding RNAs for cancer therapy.
    Forough Alemi, Fatemeh Sadeghsoltani, Khashayar Fattah, Parisa Hassanpour, Faezeh Malakoti, Sina Kardeh, Melika Izadpanah, Debora Aparecida Pires de Campos Zuccari, Bahman Yousefi, Maryam Majidinia.
      Noncoding RNAs (ncRNAs) are engaged in key cell biological and pathological events, and their expression alteration is connected to cancer progression both directly and indirectly. A huge number of studies have mentioned the significant role of ncRNAs in cancer prevention and therapy that make them an interesting subject for cancer therapy. However, there are several limitations, including delivery, uptake, and short half-life, in the application of ncRNAs in cancer treatment. Exosomes are introduced as promising options for the delivery of ncRNAs to the target cells. In this review, we will briefly discuss the application and barriers of ncRNAs. After that we will focus on exosome-based ncRNAs delivery and their advantages as well as the latest achievements in drugging ncRNAs with exosomes.
    Keywords:  Evs, extracellular vesicles; exosomes; miRNA; ncRNAs; ncRNAscancer
    DOI:  https://doi.org/10.1111/cbdd.14300
  5. Life Sci. 2023 Jul 25. pii: S0024-3205(23)00612-4. [Epub ahead of print] 121977
    Bleomycin loaded exosomes enhanced antitumor therapeutic efficacy and reduced toxicity.
    Sana Shaikh, Muhammad Younis, Shao Yingying, Tanziela Tanziela, Liudi Yuan.
       BACKGROUND: Bleomycin (BLM) is a chemotherapeutic agent with potent antitumor activity against the tumor. However, lung fibrosis is the main drawback that limits BLM use. Tumor targeted, safe, efficient and natural delivery of BLM is important to increase the effectiveness and reduce the toxic side effects. Although tumor derived Exosomes (Exo), provide a potential vehicle for in vivo drug delivery due to their cell tropism. This study primarily focuses on generating a natural delivery platform for Exo loaded with BLM and testing its therapeutic efficacy against cancer.
    METHODS: Exosomes were isolated from cancer cells and incubated with BLM. Exo were characterized by transmission electron microscopy, western blot analysis and nanoparticle tracking analysis. We performed in vitro and in vivo analyses to evaluate the effect of Exo-BLM.
    RESULTS: Exosomes loaded with BLM are highly cancer targeting and cause the cytotoxicity of tumor cells by ROS. The fluorescence images showed that Exo-BLM accumulated in cancer cells. The results revealed that Exo-BLM induces tumor cell apoptosis by the caspase pathway. In vivo, the treatment of Exo-BLM showed targeted ability and enhanced the antitumor activity.
    CONCLUSION: This study provides an avenue for specific BLM therapeutics with minimal side effects.
    Keywords:  Bleomycin; Chemotherapy; Exosomes; Targeted drug delivery; cancer
    DOI:  https://doi.org/10.1016/j.lfs.2023.121977
  6. Tissue Cell. 2023 Jul 13. pii: S0040-8166(23)00151-9. [Epub ahead of print]84 102163
    Exosomes from metastatic colon cancer cells drive the proliferation and migration of primary colon cancer through increased expression of cancer stem cell markers CD133 and DCLK1.
    K Yasodha, L Lizha Mary, Pathak Surajit, R Satish.
      The exchange of biological material between the neighbouring cells is essential for homeostasis. In pathological conditions, such as cancer, the major challenge in cancer treatment is the abnormal expression of crucial proteins and miRNA exchanged between the cancer cells through extracellular vesicles called exosomes. Clinically, it has been noticed that the primary tumour and the distal metastases are interconnected and co-dependent. The exosomes are key factors responsible for preparing the pre-metastatic niche and communicating between the tumour and the distal metastatic site. Cancer stem cells (CSCs) are a subpopulation of cancer cells with self-renewal characteristics and are shown to be responsible for metastasis. This study aims to understand the effect of metastatic cell line-derived exosomes and their regulation of CSC marker expressions on primary colon cancer cell lines. We have identified that treatment of primary colon cancer cell lines with metastatic colon cancer cell-derived exosomes has significantly increased the proliferation, colony formation, cell migration, and invasion. In addition, there was a significant increase in the number and size of spheroids following the exosomes treatment. We found that this metastatic phenotype is due to the increased expression of CD133 and DCLK1 in primary colon cancer cells.
    Keywords:  CD133; Cancer stem cell markers; DCLK1; Exosomes
    DOI:  https://doi.org/10.1016/j.tice.2023.102163
  7. Int J Mol Sci. 2023 Jul 22. pii: 11801. [Epub ahead of print]24(14):
    Influence of Extracellular Vesicles on Lung Stromal Cells during Breast Cancer Metastasis.
    Urvi Patel, David Susman, Alison L Allan.
      Breast cancer is a prominent cause of cancer diagnosis and death in women globally, with over 90% of deaths being attributed to complications that arise from metastasis. One of the common locations for breast cancer metastasis is the lung, which is associated with significant morbidity and mortality. Curative treatments for metastatic breast cancer patients are not available and the molecular mechanisms that underlie lung metastasis are not fully understood. In order to better treat these patients, identifying events that occur both prior to and during metastatic spread to the lung is essential. Several studies have demonstrated that breast cancer-derived extracellular vesicles secreted from the primary breast tumor play a key role in establishing the lung pre-metastatic niche to support colonization of metastatic tumor cells. In this review, we summarize recent work supporting the influence of extracellular vesicles on stromal components of the lung to construct the pre-metastatic niche and support metastasis. Furthermore, we discuss the potential clinical applications of utilizing extracellular vesicles for diagnosis and treatment. Together, this review highlights the dynamic nature of extracellular vesicles, their roles in breast cancer metastasis to the lung, and their value as potential biomarkers and therapeutics for cancer prevention.
    Keywords:  breast cancer; extracellular vesicles; lung metastasis; pre-metastatic niche; stromal cells
    DOI:  https://doi.org/10.3390/ijms241411801
  8. Int J Oncol. 2023 Sep;pii: 102. [Epub ahead of print]63(3):
    Modulation of PD‑L1 expression by standard therapy in head and neck cancer cell lines and exosomes.
    Annette Affolter, Kai Liebel, Luisa Tengler, Elena Seiz, Moritz Tiedtke, Alexya Azhakesan, Julia Schütz, Marie-Nicole Theodoraki, Johann Kern, Arne M Ruder, Jens Fleckenstein, Cleo-Aron Weis, Karen Bieback, Benedikt Kramer, Anne Lammert, Claudia Scherl, Nicole Rotter, Sonja Ludwig.
      Although checkpoint inhibitors (CPI) have recently extended the treatment options and improved clinical response of advanced stage head and neck squamous cell carcinoma (HNSCC), treatment success remains unpredictable. Programmed cell death ligand‑1 (PD‑L1) is a key player in immunotherapy. Tumor cells, and exosomes derived therefrom, are carriers of PD‑L1 and efficiently suppress immune responses. The aim of the present study was to analyze the influence of established therapies on PD‑L1 expression of HNSCC cell lines and their exosomes. The HNSCC cell lines, UM‑SCC‑11B, UM‑SCC‑14C and UM‑SCC‑22C were treated with fractionated radiotherapy (RT; 5x2 Gy), cisplatin (CT) and cetuximab (Cetux) as monotherapy, or combined therapy, chemoradiotherapy (CRT; RT and CT) or radioimmunotherapy (RT and Cetux). The expression of PD‑L1 and phosphorylated (p)ERK1/2 as a mediator of radioresistance were assessed using western blotting, immunohistochemistry and an ex vivo vital tissue culture model. Additionally, exosomes were isolated from concentrated supernatants of the (un‑)treated HNSCC cell lines by size exclusion chromatography. Exosomal protein expression levels of PD‑L1 were detected using western blotting and semi‑quantitative levels were calculated. The functional impact of exosomes from the (un‑)treated HNSCC cell lines on the proliferation (MTS assay) and apoptosis (Caspase 3/7 assay) of the untreated HNSCC cell lines were measured and compared. The HNSCC cell lines UM‑SCC‑11B and UM‑SCC‑22B showed strong expression of pERK1/2 and PD‑L1, respectively. RT upregulated the PD‑L1 expression in UM‑SCC‑11B and UM‑SCC‑14C and in exosomes from all three cell lines. CT alone induced PD‑L1 expression in all cell lines. CRT induced the expression of PD‑L1 in all HNSCC cell lines and exosomes from UM‑SCC‑14C and UM‑SCC‑22B. The data indicated a potential co‑regulation of PD‑L1 and activated ERK1/2, most evident in UM‑SCC‑14C. Exosomes from irradiated UM‑SCC‑14C cells protected the unirradiated cells from apoptosis by Caspase 3/7 downregulation. The present study suggested a tumor cell‑mediated regulation of PD‑L1 upon platinum‑based CRT in HNSCC and in exosomes. A co‑regulation of PD‑L1 and MAPK signaling response was hypothesized.
    Keywords:  MAPKs; cetuximab; exosomes; head and neck squamous cell carcinomas; programmed death ligand‑1; small extracellular vesicles
    DOI:  https://doi.org/10.3892/ijo.2023.5550
  9. Pharmaceutics. 2023 Jul 07. pii: 1902. [Epub ahead of print]15(7):
    Recent Progress in Extracellular Vesicle-Based Carriers for Targeted Drug Delivery in Cancer Therapy.
    Yaqin Tang, Xingyou Liu, Meng Sun, Su Xiong, Nianting Xiao, Jianchao Li, Xiao He, Jing Xie.
      Extracellular vesicles (EVs) are small, membrane-based vesicles released by cells that play a critical role in various physiological and pathological processes. They act as vehicles for transporting a variety of endogenous cargo molecules, enabling intercellular communication. Due to their natural properties, EVs have emerged as a promising "cell-free therapy" strategy for treating various diseases, including cancer. They serve as excellent carriers for different therapeutics, including nucleic acids, proteins, small molecules, and other nanomaterials. Modifying or engineering EVs can improve the efficacy, targeting, specificity, and biocompatibility of EV-based therapeutics for cancer therapy. In this review, we comprehensively outline the biogenesis, isolation, and methodologies of EVs, as well as their biological functions. We then focus on specific applications of EVs as drug carriers in cancer therapy by citing prominent recent studies. Additionally, we discuss the opportunities and challenges for using EVs as pharmaceutical drug delivery vehicles. Ultimately, we aim to provide theoretical and technical support for the development of EV-based carriers for cancer treatment.
    Keywords:  cancer therapy; drug delivery; extracellular vesicles; nanomedicine
    DOI:  https://doi.org/10.3390/pharmaceutics15071902
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