Gastric cancer-derived exosomal miR-519a-3p promotes liver metastasis by inducing intrahepatic M2-like macrophage-mediated angiogenesis

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: Oct. 10, 2022

Liver metastasis (LM) is a major obstacle to the prognosis of gastric cancer (GC) patients, but molecular mechanism underlying liver (GC-LM) remains unknown. Exosomes have been identified as an important mediator communication between tumor cells and microenvironment. Therefore, we sought investigate effects primary GC on microenvironment role exosomal microRNAs (exo-miRNA) in GC-LM.Sequential differential centrifugation, transmission electron microscopy NanoSight analysis were used extract characterize exosomes. MicroRNA sequencing GC-derived exosomes mRNA PMA-treated THP-1 identify differentially expressed miRNAs functional targets miR-519a-3p (exo-miR-519a-3p) macrophages, respectively. Tracing internalization transfer exo-miR-519a-3p observed by immunofluorescence. Tubule formation assays, aortic ring exosome-educated GC-LM model roles angiogenesis GC-LM. Luciferase reporter assay, qRT-PCR, Western blot, ELISA, flow cytometry immunofluorescence regulatory at GC-LM.The expression level serum was significantly higher patients than without LM, high indicates worse prognosis. are mainly accumulated internalized intrahepatic macrophages. Mechanistically, activates MAPK/ERK pathway targeting DUSP2, thereby causing M2-like polarization polarized macrophages accelerate inducing promoting premetastatic niche formation.Our results indicate that plays critical mediating crosstalk potential therapeutic target for

Language: Английский

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Smoking‐Induced M2‐TAMs, via circEML4 in EVs, Promote the Progression of NSCLC through ALKBH5‐Regulated m6A Modification of SOCS2 in NSCLC Cells

Advanced Science, Journal Year: 2023, Volume and Issue: 10(22)

Published: May 28, 2023

Abstract Lung cancer is a commonly diagnosed disease worldwide, with non‐small cell lung cancers (NSCLCs) accounting for ≈ 85% of cases. Cigarette smoke an environmental exposure promoting progression NSCLC, but its role poorly understood. This study reports that smoking‐induced accumulation M2‐type tumor‐associated macrophages (M2‐TAMs) surrounding NSCLC tissues promotes malignancy. Specifically, extracellular vesicles (EVs) from cigarette extract (CSE)‐induced M2 promoted malignancy cells in vitro and vivo. circEML4 EVs CSE‐induced transported to cells, where it reduced the distribution ALKBH5 nucleus by interacting Human AlkB homolog H5 (ALKBH5), resulting elevated N6‐methyladenosine (m6A) modifications. m6A‐seq RNA‐seq revealed suppressor cytokine signaling 2 (SOCS2)‐mediated activation Janus kinase‐signal transducer activator transcription (JAK‐STAT) pathway regulating m6A modification SOCS2 via ALKBH5. Down‐regulation reversed EVs‐enhanced tumorigenicity metastasis cells. Furthermore, this found smoking patients showed increase circEML4‐positive M2‐TAMs. These results indicate M2‐TAMs promote through ALKBH5‐regulated SOCS2. also reveals TAMs acts as diagnostic biomarker especially history.

Language: Английский

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The CAR macrophage cells, a novel generation of chimeric antigen-based approach against solid tumors

Biomarker Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: Nov. 28, 2023

Abstract Today, adoptive cell therapy has many successes in cancer therapy, and this subject is brilliant using chimeric antigen receptor T cells. The CAR with its FDA-approved drugs, could treat several types of hematological malignancies thus be very attractive for treating solid cancer. Unfortunately, the cannot functional cancers due to unique features. This treatment method harmful adverse effects that limit their applications, so novel treatments must use new cells like NK cells, NKT macrophage Among these innate features, are more tumor seem a better candidate prior methods. have vital roles microenvironment and, direct effect, can eliminate efficiently. In addition, being part immune system, attended sites. With high infiltration, modulations effective. review investigates last achievements CAR-macrophage future immunotherapy method.

Language: Английский

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Recent advances in the use of extracellular vesicles from adipose-derived stem cells for regenerative medical therapeutics

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: June 6, 2024

Abstract Adipose-derived stem cells (ADSCs) are a subset of mesenchymal (MSCs) isolated from adipose tissue. They possess remarkable properties, including multipotency, self-renewal, and easy clinical availability. ADSCs also capable promoting tissue regeneration through the secretion various cytokines, factors, extracellular vesicles (EVs). ADSC-derived EVs (ADSC-EVs) act as intercellular signaling mediators that encapsulate range biomolecules. These have been found to mediate therapeutic activities donor by proliferation migration effector cells, facilitating angiogenesis, modulating immunity, performing other specific functions in different tissues. Compared themselves, ADSC-EVs offer advantages such fewer safety concerns more convenient transportation storage for application. As result, these received significant attention cell-free agents with potential future application regenerative medicine. In this review, we focus on recent research progress regarding medical use across conditions, wound healing, chronic limb ischemia, myocardial infarction, diabetic nephropathy, fat graft survival, bone regeneration, cartilage tendinopathy tendon peripheral nerve acute lung injury, among others. We discuss underlying mechanisms responsible inducing effects. believe deciphering biological effects, associated will provide foundation developing novel approach Graphical

Language: Английский

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Exosomal circ_0006896 promotes AML progression via interaction with HDAC1 and restriction of antitumor immunity

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 6, 2025

Drug resistance and immune escape continue to contribute poor prognosis in AML. Increasing evidence suggests that exosomes play a crucial role AML microenvironment. Sanger sequencing, RNase R fluorescence situ hybridization were performed confirm the existence of circ_0006896. The circ_0006896 progression was assessed by vitro vivo functional experiments. Flow cytometry, RT-qPCR adoptive T cell-transfer immunotherapy conducted assess function exosomal CD8+ cell dysfunction. RNA pull-down assay, mass spectrometry, immunofluorescence, co-immunoprecipitation western blot identify interacting proteins. CircRNA expression patterns differ significantly between controls compared lncRNAs or mRNAs. A new circRNA, circ_0006896, is upregulated both cells correlates with relapse In studies suggest promotes proliferation, reduces chemotherapy sensitivity, more importantly, impairs efficacy immunotherapy. Mechanistically, physically interacts catalytic domain histone deacetylase HDAC1, decreasing H3 acetylation, impairing transcription genes involved arachidonic acid metabolism, ultimately inhibiting lipid peroxidation ferroptosis cells. Exosomal disrupts LEF1 subsequently cytotoxic molecules IFN-γ Granzyme B. We demonstrate self-driven mediated circRNAs cells, highlighting potential targeting

Language: Английский

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Exosomal lncRNA Mir100hg from lung cancer stem cells activates H3K14 lactylation to enhance metastatic activity in non-stem lung cancer cells

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 28, 2025

The mean survival of metastatic lung adenocarcinoma is less than 1 year, highlighting the urgent need to understand mechanisms underlying its high mortality rate. role Extracellular vesicles (EVs) in facilitating interactions between cancer cells and microenvironment has garnered increasing attention. Previous studies on EVs metastasis have been primarily focused cell-derived modulating functions stromal cells. However, whether stem (CSCs) can alter properties non-CSC cells, EV crosstalk mediate such interaction, not demonstrated prior this report. In present study, we integrated multi-omics sequencing public database analysis with experimental validation demonstrate, for first time, exosomal Mir100hg, derived from CSCs, could enhance potential non-CSCs both vitro vivo. Mechanistically, HNRNPF HNRNPA2B1 directly binds trafficking via exosomes non-CSCs. non-CSCs, Mir100hg upregulates ALDOA expression, subsequently leading elevated lactate production. Consequently, increased levels H3K14 lactylation by 2.5-fold promote transcription 169 metastasis-related genes. This cascade events ultimately results enhanced ALDOA-driven glycolysis histone lactylation-mediated We delineated a complex regulatory network utilized CSCs transfer their activity through providing new mechanistic insights into communication these two heterogeneous tumor cell populations. These provide novel therapeutic targets cancer, including HNRNPF/HNRNPA2B1-mediated pathway, advancing our understanding CSC-mediated while suggesting promising strategies clinical intervention.

Language: Английский

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Noncoding RNA (ncRNA)-mediated regulation of TLRs: critical regulator of inflammation in tumor microenvironment

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(5)

Published: March 31, 2025

Language: Английский

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Extracellular vesicles remodel tumor environment for cancer immunotherapy

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Dec. 13, 2023

Tumor immunotherapy has transformed neoplastic disease management, yet low response rates and immune complications persist as major challenges. Extracellular vesicles including exosomes have emerged therapeutic agents actively involved in a diverse range of pathological conditions. Mounting evidence suggests that alterations the quantity composition extracellular (EVs) contribute to remodeling immune-suppressive tumor microenvironment (TME), thereby influencing efficacy immunotherapy. This revelation sparked clinical interest utilizing EVs for sensitization. In this perspective article, we present comprehensive overview origins, generation, interplay among various components within TME. Furthermore, discuss pivotal role reshaping TME during tumorigenesis their specific cargo, such PD-1 non-coding RNA, which influence phenotypes critical cells Additionally, summarize applications different anti-tumor therapies, latest advancements engineering cancer immunotherapy, challenges encountered translation. light these findings, advocate broader understanding impact on TME, will unveil overlooked vulnerabilities potentially enhance existing immunotherapies.

Language: Английский

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Delivery of Engineered Primary Tumor-Derived Exosomes Effectively Suppressed the Colorectal Cancer Chemoresistance and Liver Metastasis

ACS Nano, Journal Year: 2023, Volume and Issue: 17(11), P. 10313 - 10326

Published: May 4, 2023

Liver metastasis is one of the major causes colorectal cancer (CRC)-related morbidity and mortality. Delivering small interfering RNAs (siRNAs) or noncoding has been reported as a promising method to target liver chemoresistance in CRC. Here, we report RNA delivery system using exosomes derived from primary patient cells. Coiled-coil domain-containing protein 80 (CCDC80) was strongly associated with CRC chemoresistance, finding validated by bioinformatic analysis clinical specimens. Silencing CCDC80 significantly increased sensitivity chemotherapy agents OXA-resistant cell lines mouse model. The cell-derived exosome designed simultaneously deliver siRNAs targeting increase distant models patient-derived xenograft models. We further antitumor effect an ex vivo model chemoresistant organoids organoid Tumor-bearing mice treated siRNA-delivering hepatectomy showed ideal overall survival. Our results provide therapeutic represent possible alternative for patients cases chemoresistance.

Language: Английский

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Potential mechanisms of cancer-associated fibroblasts in therapeutic resistance

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 166, P. 115425 - 115425

Published: Sept. 4, 2023

Despite continuous improvements in research and new cancer therapeutics, the goal of eradicating remains elusive because drug resistance. For a long time, resistance has been focused on tumor cells themselves; however, recent studies have found that microenvironment also plays an important role inducing Cancer-associated fibroblasts (CAFs) are main component microenvironment. They cross-talk with to support their survival presence anticancer drugs. This review summarizes current knowledge CAFs An in-depth understanding mechanisms underlying between insight into importance can guide development strategies.

Language: Английский

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