bims-exocan 2023-10-08 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2023–10–08
twelve papers selected by
Muhammad Rizwan, COMSATS University

Theranostic signature of tumor-derived exosomes in cancer.
Role of exosomes in prostate cancer and male fertility.
Exosomal miR-30a-5p promoted intrahepatic cholangiocarcinoma progression by increasing angiogenesis and vascular permeability in PDCD10 dependent manner.
Exosomal miRNA-166-5p derived from G-MDSCs promotes proliferation by targeting ITM3E in colorectal cancer.
The Dual Effects of Exosomes on Glioma: A Comprehensive Review.
Plasma Exosomal miRNAs as Response Biomarkers of Immunotherapy in Extensive-Stage Small-Cell Lung Cancer.
Liquid biopsy techniques and pancreatic cancer: diagnosis, monitoring, and evaluation.
The therapeutic effects of exosomes the first time isolated from pancreatic islet-derived progenitor cells in the treatment of pancreatic cancer.
Cancer-associated fibroblasts secret extracellular vesicles to support cell proliferation and epithelial-mesenchymal transition in laryngeal squamous cell carcinoma.
Exosomes-mediated transfer of LINC00691 regulates the formation of CAFs and promotes the progression of gastric cancer.
Editorial: Role of extracellular vesicles (EVs) in pathogenesis, diagnosis, therapeutic delivery, treatment and theranostic applications in cancer.
Exosomal miR-105-5p derived from bladder cancer stem cells targets for GPR12 to promote the malignancy of bladder cancer.

Med Oncol. 2023 Oct 05. 40(11): 321

Theranostic signature of tumor-derived exosomes in cancer.

Samruti Kumar, Rajib Dhar, Lokesh Babu Sirkali Suresh Kumar, Gauresh Gurudas Shivji, Rama Jayaraj, Arikketh Devi.

  Cancer is the most challenging global health crisis. In the recent times, studies on extracellular vesicles (EVs) are adding a new chapter to cancer research and reports on EVs explores cancer in a new dimension. Exosomes are a group of subpopulations of EVs. It originates from the endosomes and carries biologically active molecules to the neighboring cells which in turn transforms the recipient cell activity. In general, it plays a role in cellular communication. The correlation between exosomes and cancer is fascinating. Tumor-derived exosomes (TEXs) play a dynamic role in cancer progression and are associated with uncontrolled cell growth, angiogenesis, immune suppression, and metastasis. Its molecular cargo is an excellent source of cancer biomarkers. Several advanced molecular profiling approaches assist in exploring the TEXs in depth. This paves the way for a strong foundation for identifying and detecting more specific and efficient biomarkers. TEXs are also gaining importance in scientific society for its role in cancer therapy and several clinical trials based on TEXs is a proof of its significance. In this review, we have highlighted the role of TEXs in mediating immune cell reprogramming, cancer development, metastasis, EMT, organ-specific metastasis, and its clinical significance in cancer theranostics. TEXs profiling is an effective method to understand the complications associated with cancer leading to good health and well-being of the individual and society as a whole.

Keywords:  Cancer progression; Good health and well-being; Immunotherapy; Tumor-derived exosomes (TEXs)

DOI:  https://doi.org/10.1007/s12032-023-02176-6
Drug Discov Today. 2023 Sep 28. pii: S1359-6446(23)00307-0. [Epub ahead of print] 103791

Role of exosomes in prostate cancer and male fertility.

Dwaipayan Dey, Srestha Ghosh, Divya Mirgh, Siva Parsad Panda, Niraj Kumar Jha, Saurabh Kumar Jha.

  Prostate cancer (PCa) is the second most common and fifth most aggressive neoplasm among men worldwide. In the last decade, extracellular vesicle (EV) research has decoded multiple unsolved cancer-related mysteries. EVs can be classified as microvesicles, apoptotic bodies, and exosomes, among others. Exosomes play a key role in cellular signaling. Their internal cargos (nucleic acids, proteins, lipids) influence the recipient cell. In PCa, the exosome is the regulator of cancer progression. It is also a promising theranostics tool for PCa. Moreover, exosomes have strong participation in male fertility complications. This review aims to highlight the exosome theranostics signature in PCa and its association with male fertility.

Keywords:  exosomes; metastasis; prostate cancer; seminal exosomes; therapeutic

DOI:  https://doi.org/10.1016/j.drudis.2023.103791
Int J Biol Sci. 2023 ;19(14): 4571-4587

Exosomal miR-30a-5p promoted intrahepatic cholangiocarcinoma progression by increasing angiogenesis and vascular permeability in PDCD10 dependent manner.

Wangjie Jiang, Xiaoli Shi, Lizhu Sun, Yaodong Zhang, Xiangxu Kong, Xiao Yang, Yongmei Yin, Changxian Li, Xiangcheng Li.

  Tumor-associated angiogenesis positively associates with malignant metastasis of intrahepatic cholangiocarcinoma (ICCA). Cancer cell-derived exosomes carrying microRNAs involves in tumor microenvironment (TME) regulation. We aimed to evaluate exosomal miR-30a-5p in ICCA development. Our data showed that increased miR-30a-5p level was correlated with higher microvascular density (MVD) and worse prognosis. Augmented miR-30a-5p expression was induced by hypoxia induced factor 1α (HIF-1α) in ICCA cell. Further exploration revealed that ICCA-derived miR-30a-5p could be transferred to endothelial and increased endothelial cells recruitment and proliferation, induced angiogenesis and vascular permeability in exosome dependent manner. In addition, circulating exosomal miR-30a-5p was higher in ICCA patients, and correlated with ICCA tissues-expressing miR-30a-5p. Hypoxic stress enhanced the effects of exosomal miR-30a-5p on endothelial-associated phenotypes. Rescued experiments showed that exosomal miR-30a-5p modulated endothelial-associated phenotypes in a way relied on programmed cell death 10 (PDCD10). Moreover, we revealed that the packing of miR-30a-5p into ICCA cells-derived exosomes was mediated by eukaryotic translation initiation factor 4B (EIF4B). More importantly, the combined application of targeting miR-30a-5p and apatinib could synergistically improve antiangiogenic efficacy in ICCA. Combined, ICCA-derived exosomal miR-30a-5p could be an excellent therapeutic and monitoring indicator for ICCA patients.

Keywords:  PDCD10; angiogenesis; cholangiocarcinoma; miR-30a-5p; permeability

DOI:  https://doi.org/10.7150/ijbs.83170
Environ Toxicol. 2023 Oct 04.

Exosomal miRNA-166-5p derived from G-MDSCs promotes proliferation by targeting ITM3E in colorectal cancer.

Tao Ma, Jinling Jiang, Min Shi, Haoping Xu.

   BACKGROUND: The immune milieu of colorectal cancer is a complex phenomenon. It is imperative to investigate the crucial immune factors that promote the progression of colorectal cancer. Immune suppressor cells are granulocytic myeloid-derived suppressor cells (G-MDSCs). However, they also increased cancer growth in other ways that need to be investigated further.
METHODS: Using flow cytometry, we isolated G-MDSCs from colorectal cancer tissues. Ultracentrifugation was used to separate exosomes from the supernatant of G-MDSCs, and western blotting, transmission electron microscopy (TEM), and flow cytometry were used to confirm their presence. RNA sequencing was used to identify unique miRNAs and transcripts, which were subsequently confirmed by RT-qPCR (real-time quantitative real-time PCR). The CCK-8 test was used to determine the rate of proliferation. Lentiviral vectors were employed to manipulate the expression of miRNAs and genes in order to investigate their role in the development of colorectal cancer.
RESULTS: Colorectal cancer tissues have been found to contain granulocyte-myeloid-derived suppressor cells (G-MDSCs) that secrete exosomes. These exosomes have been shown to accelerate cancer progression by promoting cell proliferation. Further research has identified microRNA-166-5p as a target from G-MDSC-derived exosomes. This downregulation leads to the inhibition of integral membrane protein 2B (ITM3E) transcription, which in turn activates the PI3K/Akt signaling pathway. This pathway promotes cell proliferation and can be inhibited using deguelin. The accelerated development of colorectal cancer has been further confirmed in mice models.
CONCLUSION: The primary results of this work show that exosomes produced from G-MDSCs and the miR-166-5p/ITM3E axis have therapeutic and diagnostic promise in colorectal cancer.

Keywords:  G-MDSCs; ITM3E; exosomes; miRNA-166-5p; proliferation

DOI:  https://doi.org/10.1002/tox.23980
J Cancer. 2023 ;14(14): 2707-2719

The Dual Effects of Exosomes on Glioma: A Comprehensive Review.

Maowen Luo, Xingzhao Luan, Gen Jiang, Luxia Yang, Kekun Yan, Shenjie Li, Wei Xiang, Jie Zhou.

  Glioma is a frequently occurring type of cancer that affects the central nervous system. Despite the availability of standardized treatment options including surgical resection, concurrent radiotherapy, and adjuvant temozolomide (TMZ) therapy, the prognosis for glioma patients is often unfavorable. Exosomes act as vehicles for intercellular communication, contributing to tissue repair, immune modulation, and the transfer of metabolic cargo to recipient cells. However, the transmission of abnormal substances can also contribute to pathologic states such as cancer, metabolic diseases, and neurodegenerative disorders. The field of exosome research in oncology has seen significant advancements, with exosomes identified as dynamic modulators of tumor cell proliferation, migration, and invasion, as well as angiogenesis and drug resistance. Exosomes have negligible cytotoxicity, low immunogenicity, and small size, rendering them an ideal therapeutic candidate for glioma. This comprehensive review discusses the dual effects of exosomes in glioma, with an emphasis on their role in facilitating drug resistance. Furthermore, the clinical applications and current limitations of exosomes in glioma therapy are also discussed in detail.

Keywords:  Glioma; diagnosis; drug resistance.; exosome; therapy

DOI:  https://doi.org/10.7150/jca.86996
Int J Radiat Oncol Biol Phys. 2023 Oct 01. pii: S0360-3016(23)05235-5. [Epub ahead of print]117(2S): e70

Plasma Exosomal miRNAs as Response Biomarkers of Immunotherapy in Extensive-Stage Small-Cell Lung Cancer.

B Wang, J Chen, M Fan.

PURPOSE/OBJECTIVE(S): Immunotherapy combined with chemotherapy has become the first-line standard treatment for patients with extensive-stage small-cell lung cancer (ES-SCLC). The reliable biomarkers stratifying true responders of immunotherapy effectively are unknown, and it is urgent to identify novel biomarkers in clinical. Exosomal miRNAs are considered to play a role in intercellular communication among immune cells and interaction between immune cells and tumor cells. The purpose of this study was to explore the possibility of using plasma-derived exosomal miRNAs as potential biomarkers for identifying responses to immunotherapy in ES-SCLC.
MATERIALS/METHODS: From March 2020 to September 2021, 24 patients with ES-SCLC who received PD-L1 inhibitors were enrolled. Tumor assessments were conducted after every two treatment cycles according to RECIST 1.1. Plasma samples of these patients were collected before administering PD-L1 inhibitors as the baseline, and after every four cycles until the occurrence of disease progression. Plasma exosomes were isolated by ultracentrifugation, then total RNA was extracted. The miRNA profile was analyzed with small RNA next-generation sequencing followed by differential expression analysis.
RESULTS: Of the 24 patients, 15 underwent immunotherapy maintenance after completing four cycles of PD-L1 inhibitor plus chemotherapy. In order to identify biomarkers for a better response to immunotherapy, all five responders (patients achieving PR) and four non-responders (patients achieving PD) at tumor assessment within eight cycles of the maintenance phase were included for differential expression analysis. Surprisingly, hsa-miR-320c, hsa-miR-320d, and hsa-miR-320e showed a trend of increased expression in the non-responders compared with the responders at baseline and were significantly downregulated in the post-treatment plasma exosomes compared with pre-treatment samples of the responders.
CONCLUSION: Exosomal miRNA profiles are discordant between responders and non-responders of anti-PD-L1 treatment. Hsa-miR-320c, hsa-miR-320d, and hsa-miR-320e were identified as potential biomarkers for predicting the efficacy of immunotherapy in patients with ES-SCLC.

DOI: https://doi.org/10.1016/j.ijrobp.2023.06.801
Mol Cancer. 2023 Oct 06. 22(1): 167

Liquid biopsy techniques and pancreatic cancer: diagnosis, monitoring, and evaluation.

Kangchun Wang, Xin Wang, Qi Pan, Bei Zhao.

  Pancreatic cancer (PC) is one of the most common malignancies. Surgical resection is a potential curative approach for PC, but most patients are unsuitable for operations when at the time of diagnosis. Even with surgery, some patients may still experience tumour metastasis during the operation or shortly after surgery, as precise prognosis evaluation is not always possible. If patients miss the opportunity for surgery and resort to chemotherapy, they may face the challenging issue of chemotherapy resistance. In recent years, liquid biopsy has shown promising prospects in disease diagnosis, treatment monitoring, and prognosis assessment. As a noninvasive detection method, liquid biopsy offers advantages over traditional diagnostic procedures, such as tissue biopsy, in terms of both cost-effectiveness and convenience. The information provided by liquid biopsy helps clinical practitioners understand the molecular mechanisms underlying tumour occurrence and development, enabling the formulation of more precise and personalized treatment decisions for each patient. This review introduces molecular biomarkers and detection methods in liquid biopsy for PC, including circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), noncoding RNAs (ncRNAs), and extracellular vesicles (EVs) or exosomes. Additionally, we summarize the applications of liquid biopsy in the early diagnosis, treatment response, resistance assessment, and prognostic evaluation of PC.

Keywords:  Circulating tumour DNA; Circulating tumour cells; Exosomes; Extracellular vesicles; Liquid biopsy; Noncoding RNAs; Pancreatic cancer

DOI:  https://doi.org/10.1186/s12943-023-01870-3
Protoplasma. 2023 Oct 06.

The therapeutic effects of exosomes the first time isolated from pancreatic islet-derived progenitor cells in the treatment of pancreatic cancer.

Imren Hasoglu, Ayse Karatug Kacar.

  Insulinoma is an excessive insulin-released beta cell tumor. Pancreas cancer is one of the deadliest malignant neoplasms. Exosomes are secreted cell membrane vesicles containing a large number of proteins, lipids, and nucleic acids. The aim of this study is to investigate the effects of exosomes on two cell lines of benign and malignant character. For the first time, exosomes were isolated from pancreatic island-derived progenitor cells (PID-PCs) and applied to INS-1 and MiaPaCa-2 cells. In addition, exosomes isolated from PID-PC, MiaPaca-2, and INS-1 cells were characterized in order to compare their sizes with other previously isolated exosomes. Alix, TSG101, CD9, and CD81 were analyzed. The size and concentration of exosomes and the cell viability were detected. The cells were marked with HSP90, HSF-1, Kaspaz-8, Active-Kaspaz-3, Beclin, and p-Bcl-2. The cell cytotoxicity and insulin levels kit were measured. Alix in all exosomes, and PID-PC, MiaPaca-2 cell lysates; TSG101 in PID-PC and MiaPaca-2 cell lysates; CD9 in INS-1 exosomes were detected. The dimensions of isolated exosomes were 103.6 ± 28.6 nm, 100.7 ± 10 nm, and 147.2 ± 12.3 nm for PID-PCs, MiaPaca-2, and INS-1 cells. The cell viability decreased and HSP90 increased in the MiaPaca-2 cells. The HSF-1 was higher in the control MiaPaca-2 cell compared to the control INS-1 cell, and the exosome-treated MiaPaca-2 cell compared to the exosome-treated INS-1 cell. Beclin and p-Bcl-2 were decreased in the exosome-treated MiaPaca-2 cells. The insulin level in the cell lysates increased compared to cell secretion in INS-1 cells. In conclusion, exosomes isolated from the PID-PC caused cell death in the MiaPaca-2 cells in a time- and dose-dependent manner. The IC50 value determined for MiaPaca-2 cells has no effect on cell viability in INS-1 cells, which best mimics pancreatic beta cells and can be used instead of healthy pancreatic beta cells. Isolated exosomes can kill cancer cells without damaging healthy cells.

Keywords:  Cell death; Exosomes; Marker; PID-PC; Pancreatic cancer

DOI:  https://doi.org/10.1007/s00709-023-01896-w
Mol Cell Probes. 2023 Sep 28. pii: S0890-8508(23)00043-9. [Epub ahead of print] 101934

Cancer-associated fibroblasts secret extracellular vesicles to support cell proliferation and epithelial-mesenchymal transition in laryngeal squamous cell carcinoma.

Tingting Li, Linli Tian, Jing Cao, Ming Liu.

  As the critical components of tumor microenvironment, cancer-associated fibroblasts (CAFs) support the development of various type of cancers, including laryngeal squamous cell carcinoma (LSCC), but the detailed molecular mechanisms by which cancer-associated fibroblasts interact with LSCC cells to facilitate its progression have not been fully uncovered. In the present study, by analyzing the contents from normal fibroblasts (NFs) and cancer-associated fibroblasts-derived extracellular vesicles (EVs) with Real-Time qPCR analysis, we found that the tumor-initiating LncRNA TUC338 was significantly upregulated in the cancer-associated fibroblasts-derived extracellular vesicles, compared to the normal fibroblasts-secreted extracellular vesicles. Further experiments confirmed that cancer-associated fibroblasts-derived extracellular vesicles promoted cell proliferation, colony formation abilities, epithelial-mesenchymal transition (EMT) and tumorigenesis of LSCC cells via delivering LncRNA TUC338. The mechanical experiments verified that LncRNA TUC338 was stabilized by METTL3/YTHDF1-mediated N6-methyladenosine (m6A) modifications, and elevated LncRNA TUC338 sponged miR-8485 to upregulate chromobox homolog 2 (CBX2) in LSCC cells in a competing endogenous RNA mechanisms-dependent manner. Moreover, our rescue experiments evidenced that cancer-associated fibroblasts-derived LncRNA TUC338-containing extracellular vesicles-induced supportive effects in LSCC aggressiveness were all abrogated by overexpressing miR-8485 and silencing CBX2. Collectively, this study is the first to identify a novel m6A/LncRNA TUC338/miR-8485/CBX2 axis in CAFs-EVs-mediated LSCC development, and to show its potential as a diagnostic biomarker for LSCC.

Keywords:  CBX2; Cancer-associated fibroblasts; Competing endogenous RNA; Extracellular vesicles; LncRNA TUC338

DOI:  https://doi.org/10.1016/j.mcp.2023.101934
BMC Cancer. 2023 Oct 02. 23(1): 928

Exosomes-mediated transfer of LINC00691 regulates the formation of CAFs and promotes the progression of gastric cancer.

Bin Xia, Xiuyu Gu, Tingting Xu, Meina Yan, Lan Huang, Chun Jiang, Meifen Li, Guanghua Zhai, Guoping Zhang, Jian Wu, Yu Zhou, Chunrong Sun, Wei Liang.

   OBJECTIVE: Gastric cancer (GC) is one of the malignant tumors with the highest mortality worldwide. Our previous studies have revealed that LINC00691 is up-regulated in serum of GC patients as a novel potential biomarker for GC diagnosis and prognosis. However, the roles of serum exosomal LINC00691 in GC has not been clarified. This study aimed to find the expression pattern of serum exosomal LINC00691 in GC patients and the correlation between the level of serum exosomal LINC00691 and the pathology of gastric cancer patients.
METHODS: We collected the serum of 94 GC patients before surgery and extracted exosomes to detect the expression level of exosomal LINC00691, with 21 healthy volunteers and 17 patients with benign gastric diseases as controls. Surgical GC tissues and paired healthy tissues were collected to culture primary cancer-associated fibroblasts (CAFs) and normal fibroblasts (NFs). We then treated NFs with LINC00691-rich GC cell culture supernatant or exosomes and detected the activation markers and biological functions of the fibroblasts.
RESULTS: The results of real-time qPCR indicated that the serum exosomal LINC00691 of GC patients was significantly higher than that of healthy subjects and patients with benign gastric diseases, and was associated with the clinicopathology of GC patients. More interestingly, when the NFs were treated with GC exosomes, the level of LINC00691 was significantly increased, the cell proliferation and migration were noticeably enhanced, and the ability to accelerate GC cell proliferation and invasion was promoted, which means that the induced fibroblasts gained the properties of CAFs. In addition, we found that knockdown of LINC00691 and the use of the JAK2/STAT3 signaling pathway inhibitor ruxolitinib effectively deprived exosome-containing GC cell supernatants of the effects on NFs.
CONCLUSION: Our study suggested that exosomal LINC00691 promoted NFs to gained the properties of CAFs depending on JAK2/STAT3 signaling pathway as a potential diagnostic biomarker for GC.

Keywords:  Cancer-associated fibroblasts; Exosomes; Gastric cancer; Normal fibroblasts; lncRNAs

DOI:  https://doi.org/10.1186/s12885-023-11373-5
Front Bioeng Biotechnol. 2023 ;11 1288806

Editorial: Role of extracellular vesicles (EVs) in pathogenesis, diagnosis, therapeutic delivery, treatment and theranostic applications in cancer.

Reza Shahbazi, Kalimuthu Kalishwaralal, Manash K Paul, Ruby John Anto.



Keywords:  bacterial exosome; cancer; exosomes; extracellular vesicles; plant exosome; proteomics

DOI:  https://doi.org/10.3389/fbioe.2023.1288806
BMC Urol. 2023 Oct 03. 23(1): 155

Exosomal miR-105-5p derived from bladder cancer stem cells targets for GPR12 to promote the malignancy of bladder cancer.

Gaojian Pan, Bo Jiang, Zhongquan Yi, Jiuhu Yin, Yadong Liu.

  Bladder cancer stem cells (BCSCs) are considered as the root cause of BC initiation and recurrence, and exosomes derived from BCSCs (CSCs-exo) are the vital tool for establishing a stable tumor microenvironment. miR-105-5p has been revealed to promote tumor growth in a variety of cancers, but the effects on BC are still not included.Characteristics of CSCs-exo were examined by transmission electron microscope and nanoparticle tracking analysis. PKH67 dye was used to observe the cellular uptake of exosomes. Cell viability, migration and invasion were detected by CCK-8, wound healing and transwell invasion assays, respectively. The interaction between miR-105-5p and GPR12 was verified by luciferase activity assay. Xenografts were induced in the nude mice, and H&E staining method was applied to analyze the histological changes of xenografts. CSCs-exo efficiently promoted BC cell viability, migration and invasion. miR-105-5p was highly expressed in CSCs and CSCs-exo treatment significantly upregulated the expression of miR-105-5p in BC cells.GPR12 was subsequently verified to be the target gene of miR-105-5p, and overexpression of GPR12 abrogated the effects of miR-105-5p on BC cell growth and metastasis. Reversely, the anti-tumor function of miR-105-5p antagomir was observed in the xenograft mice.CSCs aggravated the malignancy of BC partly through transmitting exosomal miR-105-5p to BC cells to inhibit the expression of GPR12, which developed a novel aspect for CSC-targeted therapies.

Keywords:  Bladder cancer; Cancer stem cell; Exosome; GPR12; miR-105-5p

DOI:  https://doi.org/10.1186/s12894-023-01326-2