bims-exocan 2023-10-15 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2023–10–15
eleven papers selected by
Muhammad Rizwan, COMSATS University

Exosome, the glass slipper for Cinderella of cancer-bladder cancer?
Haematopoietic cell-derived exosomes in cancer development and therapeutics: From basic science to clinical practice.
Immunotherapeutic effect of photothermal-mediated exosomes secreted from breast cancer cells.
Cancer-Associated Fibroblasts Boost Tumorigenesis of Clear Cell Renal Cell Carcinoma via Exosome-Mediated Paracrine SNHG1.
Role of exosomes in prostate cancer bone metastasis.
Exosomes: Emerging Modulators of Pancreatic Cancer Drug Resistance.
Exosomes secreted by metastatic cancer cells promotes epithelial mesenchymal transition in small cell lung carcinoma: the key role of Src/TGF-β1 axis.
Exosome miRNA-203 promotes M1 macrophage polarization and inhibits prostate cancer tumor progression.
Urinary exosomal tRNA-derived small RNA signatures as a predictive biomarker in lung cancer.
The Emerging Role of Exosomal miRNAs as Biomarkers for Early Cancer Detection: A Comprehensive Literature Review.
Regulations of Exosomal-Transmitted AFAP1-AS1 LncRNA on Ovarian Cancer Cell Migration and Invasion.

J Nanobiotechnology. 2023 Oct 07. 21(1): 368

Exosome, the glass slipper for Cinderella of cancer-bladder cancer?

Yuanyuan Yang, Lintao Miao, Yuchao Lu, Yi Sun, Shaogang Wang.

  Exosomes are lipid bilayer vesicles with a diameter of 40-100 nm secreted by almost all cells. They have been found play crucial regulatory roles in various diseases. With the development of exosomes engineering technology, exosome-based drug delivery has also rapidly evolved. Bladder cancer is a worldwide disease with high morbidity and recurrence but lack of funding, so it is also called Cinderella. Some explorations have demonstrated that exosomes are important in the development, prognosis, diagnosis and drug delivery of bladder cancer. With the rapid development of Mass spectrometry and next-generation sequencing, increasing numbers of differentially expressed molecules derived from exosomes have been found in bladder cancer. Exosomes and their contents are largely involved in bladder cancer progression, engineering of these exosomes with the targeted genes improves their potential for drug delivery of bladder cancer. Furthermore, exosomes and their contents are relate to many characteristics of bladder cancer. Herein, we briefly search 59 researches to explore the cargoes encapsuled in exosomes of bladder cancer patients. We also summarize the biogenesis, function, expression profiles, engineering approaches and biological mechanisms of exosomes and their contents for the diagnosis, prognosis and drug delivery for bladder cancer. We aim to make it clear whether exosomes are the glass slippers of Cinderella.

Keywords:  Bladder cancer; Clinical biomarker; Exosome; Mechanism

DOI:  https://doi.org/10.1186/s12951-023-02130-8
Clin Transl Med. 2023 Oct;13(10): e1448

Haematopoietic cell-derived exosomes in cancer development and therapeutics: From basic science to clinical practice.

Wen-Chun Lin, You-Tong Lin, Hui-Ching Chao, Yen-Yu Lin, Wei-Lun Hwang.

   BACKGROUND: The tumour microenvironment (TME) is a specialised niche involving intercellular communication among cancer cells and various host cells. Among the host cells, the quantity and quality of immune cells within the TME play essential roles in cancer development and management. The immunologically suppressive, so-called 'cold' TME established by a series of tumour-host interactions, including generating immunosuppressive cytokines and recruiting regulatory host immune cells, is associated with resistance to therapies and worse clinical outcomes.
MAIN BODY: Various therapeutic approaches have been used to target the cold TME, including immune checkpoint blockade therapy and adoptive T-cell transfer. A promising, less explored therapeutic strategy involves targeting TME-associated exosomes. Exosomes are nanometer-sized, extracellular vesicles that transfer material from donor to recipient cells. These particles can reprogram the recipient cells and modulate the TME. In particular, exosomes from haematopoietic cells are known to promote or suppress cancer progression under specific conditions. Understanding the effects of haematopoietic cell-secreted exosomes may foster the development of therapeutic exosomes (tExos) for personalised cancer treatment. However, the development of exosome-based therapies has unique challenges, including scalable production, purification, storage and delivery of exosomes and controlling batch variations. Clinical trials are being conducted to verify the safety, feasibility, availability and efficacy of tExos.
CONCLUSION: This review summarises our understanding of how haematopoietic cell-secreted exosomes regulate the TME and antitumour immunity and highlights present challenges and solutions for haematopoietic cell-derived exosome-based therapies.

Keywords:  blood exosomes; cancer therapeutics; exosome engineering; tumour microenvironment

DOI:  https://doi.org/10.1002/ctm2.1448
Nanomedicine (Lond). 2023 Oct 10.

Immunotherapeutic effect of photothermal-mediated exosomes secreted from breast cancer cells.

Meysam Najaflou, Farhad Bani, Ahmad Yari Khosroushahi.

  Aim: Exosomal damage-associated molecular patterns can play a key role in immunostimulation and changing the cold tumor microenvironment to hot. Materials & methods: This study examined the immunostimulation effect of photothermal and hyperthermia-treated 4T1 cell-derived exosomes on 4T1 cell-induced breast tumors in BALB/c animal models. Exosomes were characterized for HSP70, HSP90 and HMGB-1 before injection into mice and tumor tissues were analyzed for IL-6, IL-12 and IL-1β, CD4 and CD8 T-cell permeability, and PD-L1 expression. Results: Thermal treatments increased high damage-associated molecular patterns containing exosome secretion and the permeability of T cells to tumors, leading to tumor growth inhibition. Conclusion: Photothermal-derived exosomes showed higher damage-associated molecular patterns than hyperthermia with a higher immunostimulation and inhibiting tumor growth effect.

Keywords:  PTT; cancer; cancer immunotherapy; cancer therapy side effect; exosomes; hyperthermia; photothermal therapy

DOI:  https://doi.org/10.2217/nnm-2023-0014
Biochem Genet. 2023 Oct 10.

Cancer-Associated Fibroblasts Boost Tumorigenesis of Clear Cell Renal Cell Carcinoma via Exosome-Mediated Paracrine SNHG1.

Pei Tian, Jinxing Wei, Jing Li, Junkai Ren, Chaohong He.

  Despite the dominant roles of cancer-associated fibroblasts (CAFs) have attached much attention in tumorigenesis, the CAFs-derived molecular determinants that regulate renal cell carcinoma (RCC) development remains elusive. Our previous study uncovered an oncogenic SNHG1 in the immune escape of RCC, whereas CAFs-derived exosomes could be a source accounting for increasing SNHG1 in RCC cells, this is still a mystery. The obtained CAFs and normal fibroblast (NFs) from fresh RCC and adjacent tissues were firstly identified using western blot and immunofluorescent staining. The enrichment of SNHG1 was validated by RT-qPCR. CAFs-derived exosomes were isolated from conditioned medium using ultracentrifugation method and ExoQuick-TC system. The internalization of exosomes, transfer of SNHG1, was measured by immunofluorescence. Regulation of conditioned medium or exosomal SNHG1 from CAFs on RCC biological functions was evaluated by CCK-8, EdU incorporation, colony formation, and transwell assays to assess the RCC cell proliferation, migration, and invasion. SNHG1 was significantly upregulated in CAFs isolated from RCC stroma. Exosomes derived from CAFs transferred SNHG1 to RCC cells and resulted in an increased SNHG1 expression in RCC cells. The exosomes excreted by CAFs promoted RCC cell proliferation, migration, and invasion, whereas the promotion effect of CAFs-exosomes on RCC progression was attenuated by SNHG1 knockdown. The present study revealed a new mechanism of exosomal SNHG1 extracted from CAFs enhanced RCC progression and may provide a potential target for the treatment of RCC.

Keywords:  Cancer-associated fibroblast; Exosome; Renal cell carcinoma; SNHG1

DOI:  https://doi.org/10.1007/s10528-023-10512-8
Arch Biochem Biophys. 2023 Oct 08. pii: S0003-9861(23)00283-7. [Epub ahead of print]748 109784

Role of exosomes in prostate cancer bone metastasis.

Tingting Lv, Zijie Li, Dehua Wang, Xiaojin Guo, Xiaokuan Zhang, Jing Cao, Zhiyu Wang.

  Bone is a preferred metastatic site of prostate cancer (PCa), and most patients with PCa metastases develop osteogenic bone metastasis, which manifests as disturbed bone structure and poor bone quality. However, the underlying mechanisms of PCa bone metastasis remain unclear. In recent years, increasing evidence has implicated extracellular vesicles, especially exosomes, in PCa bone metastasis. Exosomes are 30-150 nm in diameter, enclosing a cargo of biomolecules, such as DNA, RNA, and proteins. Exosomes play a functional role in intercellular communication, modulate the functions of recipient cells, and potentially modulate bone microenvironment changes, thereby influencing the development of PCa bone metastasis. This review summarizes the involvement of exosomes in the imbalance between bone resorption and formation, and establishing a pre-metastatic niche in bone marrow, as well as potential clinical applications of exosomes in therapeutic strategies for treating patients with advanced PCa with bone metastasis.

Keywords:  Bone metastasis; Bone microenvironment; Exosomes; Pre-metastatic niche; Prostate cancer

DOI:  https://doi.org/10.1016/j.abb.2023.109784
Cancers (Basel). 2023 Sep 25. pii: 4714. [Epub ahead of print]15(19):

Exosomes: Emerging Modulators of Pancreatic Cancer Drug Resistance.

Marzia Di Donato, Nicola Medici, Antimo Migliaccio, Gabriella Castoria, Pia Giovannelli.

  Pancreatic cancer (PaC) is one of the most lethal tumors worldwide, difficult to diagnose, and with inadequate therapeutical chances. The most used therapy is gemcitabine, alone or in combination with nanoparticle albumin-bound paclitaxel (nab-paclitaxel), and the multidrug FOLFIRINOX. Unfortunately, PaC develops resistance early, thus reducing the already poor life expectancy of patients. The mechanisms responsible for drug resistance are not fully elucidated, and exosomes seem to be actively involved in this phenomenon, thanks to their ability to transfer molecules regulating this process from drug-resistant to drug-sensitive PaC cells. These extracellular vesicles are released by both normal and cancer cells and seem to be essential mediators of intercellular communications, especially in cancer, where they are secreted at very high numbers. This review illustrates the role of exosomes in PaC drug resistance. This manuscript first provides an overview of the pharmacological approaches used in PaC and, in the last part, focuses on the mechanisms exploited by the exosomes released by cancer cells to induce drug resistance.

Keywords:  exosomes in pancreatic cancer; gemcitabine resistance; pancreatic cancer drug resistance

DOI:  https://doi.org/10.3390/cancers15194714
Gene. 2023 Oct 11. pii: S0378-1119(23)00714-X. [Epub ahead of print] 147873

Exosomes secreted by metastatic cancer cells promotes epithelial mesenchymal transition in small cell lung carcinoma: the key role of Src/TGF-β1 axis.

Yuzhou Shen, Jicheng TanTai.

  Exosome-mediated epithelial mesenchymal transition (EMT) is key to cancer metastasis. c-Src is involved in the secretion of exosomes and initiation of EMT. Effects of exosomes from metastatic non-small cell lung carcinoma (NSCLC) cells on the EMT process in primary NSCLC cells were assessed. Levels of c-Src in NSCLC tissues were detected and the influence of exosomes from metastatic NSCLC cells on the exosome secretion and EMT process in primary NSCLC cells was assessed. The expression of c-Src was modulated, and the influence on the secretion of exosomes and EMT initiation was evaluated. The level of c-Src was higher in NSCLC specimen and NSCLC cells with promoted EMT process. The suppression of c-Src inhibited secretion of exosomes. Exosomes from metastatic NSCLC cells enhanced migration and invasion abilities of primary NSCLC cells, which had identical effects to c-Src overexpression. The suppression of c-Src inhibited growth and metastasis of solid tumors as well as secretion of exosomes, while the injection of exosomes with c-Src overexpression promoted lung metastasis. TGF-β1 restored the invasion and migration abilities even with c-Src knockdown. The exosomes from metastatic NSCLC cells with high c-Src expression of can increase c-Src level in primary NSCLC cells, contributing to the promoted EMT process through TGF-β1 pathway.

Keywords:  TGF-β1; c-Src; epithelial mesenchymal transition; exosome; non-small cell lung carcinoma

DOI:  https://doi.org/10.1016/j.gene.2023.147873
Mol Cell Biochem. 2023 Oct 09.

Exosome miRNA-203 promotes M1 macrophage polarization and inhibits prostate cancer tumor progression.

Lian-Sheng Zhang, Qi-Chao Chen, Hong-Tao Zong, Qiang Xia.

  Prostate cancer (PCa) is a prevalent malignant neoplasm affecting the male reproductive system globally. However, the diagnostic and therapeutic approaches fall short of meeting the demands posed by PCa. Poor expression of miRNA-203 (miR-203) within PCa tissues and cells implies its potential utility as a diagnostic indicator for PCa. Exosomes (Exo), membranous vesicles released by various cells, are rich reservoirs of miRNAs. However, the presence of miR-203 presents within Exo derived from PCa cells remains unclarified. In this study, Exo was isolated from urine specimens collected from clinical PCa patients and LNCaP cells to detect miR-203 expression. Meanwhile, the impact of overexpressed miR-203 on M0 macrophages (mø) was analyzed. Subsequently, alterations in the proliferative, migratory, and invasive capacities of LNCaP cells were examined within a co-culture system featuring elevated miR-203 levels in both macrophages and LNCaP cells. Furthermore, the repercussions of miR-203 upregulation or inhibition were explored in a murine PCa tumor model. The results revealed that Exo manifested a circular or elliptical morphology, encapsulating a phospholipid bilayer approximately 100 nm in diameter. Notably, Exo readily infiltrated, with both Exo and miR-203-overexpressing Exo prompting macrophage polarization toward the M1 subtype. In the co-culture system, miR-203 exhibited pronounced suppression of LNCaP cell proliferation, migration, and invasion, while concurrently fostering apoptosis as compared with the LNCaP group (Control). In vivo experiments further disclosed that miR-203 greatly inhibited the growth of PCa tumors in nude mice. Markedly heightened expression of M1 macrophage markers such as IL-1β, IL-6, IL-12, CXCL9, and CXCL10 was observed within the tumor microenvironment following miR-203 intervention, as opposed to the model group. However, the introduction of miR-203 antagomir led to a reversal in tumor growth trends. This investigation indicates the presence of miR-203 within the urine of PCa patients and Exo originating from cells, and that miR-203 exerted antitumor effect by facilitating M1 macrophage polarization. Our study furnishes valuable insights into the potential applicability of miR-203 as a diagnostic biomarker and therapeutic target for PCa.

Keywords:  Exosomes; M1 macrophage; Prostatic cancer; Tumor microenvironment; Tumor-associated macrophage; miRNA-203

DOI:  https://doi.org/10.1007/s11010-023-04854-5
FEBS Open Bio. 2023 Oct 09.

Urinary exosomal tRNA-derived small RNA signatures as a predictive biomarker in lung cancer.

JunFeng Wang, Fenghai Ren, Yanbo Wang, JinLiang Yang.

  The use of noninvasive biomarkers may enhance the efficiency of early diagnosis for lung cancer and improve its survival rate. In this study, we investigated the possibility of utilising differential expression of NSCLC-related tsRNAs in urinary exosomes to diagnose lung cancer. Initially, the NSCLC-related tsRNAs were identified in both cancerous and normal tissue derived from the TCGA database. Subsequently, we utilized a machine learning model and ROC curves to identify the most significant tsRNAs for diagnosing NSCLC. Three tsRNAs were found to be significantly increased and were evaluated in both normal bronchial epithelium cell lines and lung cancer cell lines. Finally, we determined the presence of these three tsRNAs in urinary exosomes and demonstrated their potential as biomarkers for diagnosing NSCLC.

Keywords:  NSCLC; biomarker; exosome; tsRNA; urine

DOI:  https://doi.org/10.1002/2211-5463.13716
Technol Cancer Res Treat. 2023 Jan-Dec;22:22 15330338231205999

The Emerging Role of Exosomal miRNAs as Biomarkers for Early Cancer Detection: A Comprehensive Literature Review.

Ali Jafari, Keyvan Karimabadi, Aso Rahimi, Gelavizh Rostaminasab, Mozafar Khazaei, Leila Rezakhani, Touraj Ahmadi Jouybari.

  A significant number of cancer-related deaths are recorded globally each year, despite attempts to cure this illness. Medical science is working to develop new medication therapies as well as to find ways to identify this illness as early as possible, even using noninvasive techniques. Early detection of cancer can greatly aid its treatment. Studies into cancer diagnosis and therapy have recently shifted their focus to exosome (EXO) biomarkers, which comprise numerous RNA and proteins. EXOs are minuscule goblet vesicles that have a width of 30 to 140 nm and are released by a variety of cells, including immune, stem, and tumor cells, as well as bodily fluids. According to a growing body of research, EXOs, and cancer appear to be related. EXOs from tumors play a role in the genetic information transfer between tumor and basal cells, which controls angiogenesis and fosters tumor development and spread. To identify malignant activities early on, microRNAs (miRNAs) from cancers can be extracted from circulatory system EXOs. Specific markers can be used to identify cancer-derived EXOs containing miRNAs, which may be more reliable and precise for early detection. Conventional solid biopsy has become increasingly limited as precision and personalized medicine has advanced, while liquid biopsy offers a viable platform for noninvasive diagnosis and prognosis. Therefore, the use of body fluids such as serum, plasma, urine, and salivary secretions can help find cancer biomarkers using technologies related to EXOs.

Keywords:  biomarker; cancer; diagnosis; exosome; microRNAs

DOI:  https://doi.org/10.1177/15330338231205999
Discov Med. 2023 Oct;35(178): 877-886

Regulations of Exosomal-Transmitted AFAP1-AS1 LncRNA on Ovarian Cancer Cell Migration and Invasion.

Fuqun Zhou, Xiaohui Xu, Weidong Wei, Xiang Chen, Liying Sun.

   BACKGROUND: Adolescent ovarian cancer (OC) has high malignancy. Long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of various malignancies, but their role in adolescent OC remains poorly understood. This study aims to assess the modulatory role of Exosome-transmitted lncRNA Actin filament-associated protein 1 Antisense RNA 1 (AFAP1-AS1) on the activity of OC cells.
METHODS: We recruited a cohort of 40 adolescent patients diagnosed with OC and a control group of 40 healthy individuals. Serum samples were collected from both groups prior surgical intervention. Exosomes from peripheral blood and ascites were collected via differential centrifugation. The expression levels of AFAP1-AS1 in OC tissues and cell lines (IOSE-80, CAOV3, and SKOV3) were quantified using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The exosomal particle size and surface markers were characterized through nanoparticle tracking analysis and transmission electron microscopy. Furthermore, siRNA-mediated knockdown of AFAP1-AS1 was performed in IOSE-80, CAOV3, and SKOV3 cell lines. Functional assays, including wound-healing experiments and Transwell migration assays, were conducted to evaluate cellular migration and metastasis.
RESULTS: Our findings demonstrate that the expression of AFAP1-AS1 is significantly upregulated in OC patients' serum exosomes and ascitic fluid, correlating with unfavorable pathological features such as advanced federation international of gynecology and obstetrics (FIGO) stage and larger tumor diameter. In-vitro experiments revealed that OC cell lines and primary human OC cells showed enhanced proliferation and metastasis when exposed to ascites-derived exosomes enriched in AFAP1-AS1. Importantly, we observed that AFAP1-AS1 can be transmitted to neighboring cells via exosomal pathways. Additionally, exosomes isolated from ascites treated with siRNA targeting AFAP1-AS1 can inhibit cellular migration and invasion.
CONCLUSIONS: Our data provide evidence for the oncogenic role of AFAP1-AS1, which is transmitted via exosomes. This finding has significant implications for understanding the molecular mechanisms of AFAP1-AS1 in the pathogenesis of adolescent ovarian cancer.

Keywords:  adolescent ovarian cancer; cell metastasis; cell migration; exosomes; invasion; lncRNA AFAP1-AS1

DOI:  https://doi.org/10.24976/Discov.Med.202335178.83