Exosome-mediated metabolic reprogramming: the emerging role in tumor microenvironment remodeling and its influence on cancer progression

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Oct. 19, 2020

Abstract Metabolic reprogramming is reported to be one of the hallmarks cancer, which an adaptive mechanism by fast-growing cancer cells adapt their increasing energy demands. Recently, extracellular vesicles (EVs) known as exosomes have been recognized crucial signaling mediators in regulating tumor microenvironment (TME). Meanwhile, TME a highly heterogeneous ecosystem incorporating cells, fibroblasts, adipocytes, endothelial mesenchymal stem and matrix. Accumulated evidence indicates that may transfer biologically functional molecules recipient facilitate progression, angiogenesis, metastasis, drug resistance, immunosuppression metabolism surrounding stromal cells. In this review, we present role underlying how exacerbate development through metabolic reprogramming. addition, will also discuss potential targeting process biomarkers for diagnosis prognosis, exosomes-mediated targets therapy. Furthermore, better understanding link between reprogramming, impact on would provide novel insights prevention treatment future.

Language: Английский

---

Exosomes promote pre-metastatic niche formation in ovarian cancer

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: Aug. 13, 2019

Ovarian cancer is one of the most common gynecological malignancies. Upon initial diagnosis, majority patients present with widespread metastatic growth within peritoneal cavity. This occurs in stages, formation a pre-metastatic niche occurring prior to macroscopic tumor cell invasion. Exosomes released by primary ovarian are small extracellular vesicles which prepare distant microenvironment for accelerated They regulate intercellular communication between cells and normal stroma, cancer-associated fibroblasts, local immune microenvironment. In this review, we highlight emerging roles exosomes as coordinators formation, biomarkers amenable liquid biopsy, targets chemotherapy.

Language: Английский

---

MDSCs: Key Criminals of Tumor Pre-metastatic Niche Formation

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: Feb. 6, 2019

The emergence of disseminated metastases remains the primary cause mortality in cancer patients. Formation pre-metastatic niche (PMN), which precedes establishment tumor lesions, is critical for metastases. Bone marrow-derived myeloid cells (BMDCs) are indispensable PMN formation. Myeloid-derived suppressor (MDSCs) a population immature that accumulate patients with and appear early PMN. mechanisms by MDSCs establish microenvironment distant organs largely unknown, although play an essential role metastasis. Here, we summarize key factors associated recruitment activation review regulate formation evolution. Finally, predict potential value detection therapy.

Language: Английский

---

Supramolecular Nanofibers Containing Arginine-Glycine-Aspartate (RGD) Peptides Boost Therapeutic Efficacy of Extracellular Vesicles in Kidney Repair

ACS Nano, Journal Year: 2020, Volume and Issue: 14(9), P. 12133 - 12147

Published: Aug. 11, 2020

Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSC-EVs) have been recognized as a promising cell-free therapy for acute kidney injury (AKI), which avoids safety concerns associated with direct cell engraftment. However, low stability and retention of MSC-EVs limited their therapeutic efficacy. RGD (Arg-Gly-Asp) peptide binds strongly to integrins, identified on the surface MSC-EV membranes; yet has not applied EV scaffolds enhance prolong bioavailability. Here, we developed hydrogels, hypothesized could augment efficacy in treatment AKI models. In vivo tracking labeled EVs revealed that hydrogels increased EVs. Integrin gene knockdown experiments confirmed EV–hydrogel interaction was mediated by RGD–integrin binding. Upon intrarenal injection into mouse models, EV-RGD provided superior rescuing effects renal function, attenuated histopathological damage, decreased tubular injury, promoted proliferation early phases AKI. also augmented antifibrotic chronic stages. Further analysis presence microRNA let-7a-5p served mechanism contributing reduced apoptosis elevated autophagy conclusion, facilitated MSC-derived let-7a-5p-containing EVs, improving reparative potential against This study an scaffold increase integrin-mediated loading turn improved repair; therefore this strategy shed light application potentiated efficiency.

Language: Английский

---

Bioactive DNA from extracellular vesicles and particles

Cell Death and Disease, Journal Year: 2020, Volume and Issue: 11(7)

Published: July 27, 2020

Abstract Extracellular vesicles (EVs) and particles (EPs) have recently emerged as active carriers of molecular biomarkers mediators intercellular communication. While most investigations focused exclusively on the protein, lipid RNA constituents these extracellular entities, EV/EP DNA remains poorly understood, despite being found in association with virtually all populations. The functional potential has been proposed a number pathological states, including malignancies autoimmune diseases. Moreover, effectiveness cell-free biomarker choice emerging liquid biopsy applications highlights role that may play novel disease biomarker. In this review, we provide comprehensive overview studies conducted to date, particular focus roles mediator various pathologic states. We also review what is currently known about origins, structure, localisation distribution DNA, highlighting current controversies well opportunities for future investigation.

Language: Английский

---

Exosomal miRNAs in tumor microenvironment

Journal of Experimental & Clinical Cancer Research, Journal Year: 2020, Volume and Issue: 39(1)

Published: April 16, 2020

Tumor microenvironment (TME) is the internal environment in which tumor cells survive, consisting of cells, fibroblasts, endothelial and immune as well non-cellular components, such exosomes cytokines. Exosomes are tiny extracellular vesicles (40-160nm) containing active substances, proteins, lipids nucleic acids. carry biologically miRNAs to shuttle between TME, thereby affecting development. Tumor-derived exosomal induce matrix reprogramming creating a that conducive growth, metastasis, escape chemotherapy resistance. In this review, we updated role process TME reshaping.

Language: Английский

---

Exosome-Based Vaccines: History, Current State, and Clinical Trials

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: July 14, 2021

Extracellular vesicles (EVs) are released by most cell types as part of an intracellular communication system in crucial processes such inflammation, proliferation, and immune response. However, EVs have also been implicated the pathogenesis several diseases, cancer numerous infectious diseases. An important feature is their ability to deliver a wide range molecules nearby targets or over long distances, which allows mediation different biological functions. This delivery mechanism can be utilized for development therapeutic strategies, vaccination. Here, we highlighted studies from historical perspective, with respect current investigations on EV-based vaccines. For example, vaccines based exosomes derived dendritic cells proved simpler terms management cost-effectiveness than Recent evidence suggests that leveraged therapeutics induce strong anti-tumor responses. Moreover, shown exciting promising results against We summarized obtained completed clinical trials conducted usage exosome-based treatment cancer, more recently, coronavirus disease.

Language: Английский

---

Tumor-derived small extracellular vesicles in cancer invasion and metastasis: molecular mechanisms, and clinical significance

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Jan. 19, 2024

Abstract The production and release of tumor-derived small extracellular vesicles (TDSEVs) from cancerous cells play a pivotal role in the propagation cancer, through genetic biological communication with healthy cells. TDSEVs are known to orchestrate invasion-metastasis cascade via diverse pathways. Regulation early metastasis processes, pre-metastatic niche formation, immune system regulation, angiogenesis initiation, matrix (ECM) remodeling, modulation, epithelial-mesenchymal transition (EMT) among pathways regulated by TDSEVs. MicroRNAs (miRs) carried within as double-edged sword can either promote or inhibit cancer progression. serve excellent markers for detection tumors, tumor metastases. From therapeutic point view, risk may be reduced limiting On other hand, represent promising approach vivo delivery cargo present review article discusses recent developments current views field research clinical applications.

Language: Английский

---

Clinical significance of exosomes as potential biomarkers in cancer

World Journal of Clinical Cases, Journal Year: 2019, Volume and Issue: 7(2), P. 171 - 190

Published: Jan. 26, 2019

Exosomes are microvesicles, measuring 30-100 nm in diameter. They widely distributed body fluids, including blood, bile, urine and saliva. Cancer-derived exosomes carry a wide variety of DNA, RNA, proteins lipids, may serve as novel biomarkers cancer.To summarize the performance exosomal cancer diagnosis prognosis.Relevant publications literature were identified by search "PubMed" database up to September 11, 2018. The quality included studies was assessed QUADAS-2 REMARK. For assessment diagnostic biomarkers, 47 2240 patients from 30 included.Our results suggested that these had excellent ability various types cancer, with good sensitivity specificity. prognostic markers, 50 4797 42 included. We observed values overall survival, disease-free survival recurrence-free survival.Exosomes can function potential prognosis.

Language: Английский

---

Tumor-derived exosomal miR-3157-3p promotes angiogenesis, vascular permeability and metastasis by targeting TIMP/KLF2 in non-small cell lung cancer

Cell Death and Disease, Journal Year: 2021, Volume and Issue: 12(9)

Published: Sept. 8, 2021

Metastasis is the main cause of death in patients with advanced lung cancer. The exosomes released by cancer cells create tumor microenvironment, and then accelerate metastasis. Cancer-derived are considered to be driving force for metastasis niche formation at foreign sites, but mechanism Non-small cell carcinoma (NSCLC) unclear. In metastatic NSCLC patients, expression level miR-3157-3p circulating was significantly higher than that non-metastatic patients. Here, we found can transferred from vascular endothelial through exosomes. Our work indicates exosome involved pre-metastatic before may used as a blood-based biomarker Exosome has regulated VEGF/MMP2/MMP9 occludin targeting TIMP/KLF2, thereby promoted angiogenesis increased permeability. addition, vivo.

Language: Английский

---