Gastric cancer-derived exosomal let-7 g-5p mediated by SERPINE1 promotes macrophage M2 polarization and gastric cancer progression

Journal of Experimental & Clinical Cancer Research, Год журнала: 2025, Номер 44(1)

Опубликована: Янв. 2, 2025

Abstract Background Tumor-associated macrophages (TAMs), particularly M2-polarized TAMs, are significant contributors to tumor progression, immune evasion, and therapy resistance in gastric cancer (GC). Despite efforts target TAM recruitment or depletion, clinical efficacy remains limited. Consequently, the identification of targets that specifically inhibit reprogram TAMs presents a promising therapeutic strategy. Objective This study aims identify dual-function GC cells drives both malignant phenotypes M2 macrophage polarization, revealing its molecular mechanisms provide novel for selectivly targeting GC. Methods Transcriptomic data from adjacent tissues were utilized mRNAs associated with high infiltration poor prognosis. Single-cell sequencing elucidated cell types expressing gene. Transwell co-culture exosome intervention experiments demonstrated role polarization. Small RNA exosomes, western blotting, CoIP assays revealed underlying exosome-mediated Protein array, ChIP dual-luciferase reporter clarified by which gene regulated exosomal miRNA. In vivo validation was performed using xenograft models. Results SERPINE1 identified as highly expressed mRNA cells, significantly advanced stages, worse prognosis, higher patients overexpression promoted growth facilitated transfer let-7 g-5p via cancer-derived inducing Exosomal internalized downregulated SOCS7 protein levels, disrupting interaction STAT3 relieving inhibition phosphorylation, thereby leading hyperactivation, consequently drove Additionally, elevated expression activated JAK2, enhancing binding promoter promoting transcription, increasing levels exosomes. Conclusion cell-derived , functioning primary driver promotes polarization through regulation autocrine activation JAK2/STAT3 signaling pathway. These findings elucidate mechanism -induced highlight advancing immunotherapy targeted treatments

Язык: Английский

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Effect of Extracellular Vesicles Derived From Tumor Cells on Immune Evasion

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Фев. 3, 2025

The crosstalk between immunity and cancer in the regulation of tumor growth is considered a hallmark cancer. Antitumor refers to innate adaptive immune responses that regulate development proliferation. Tumor evasion represents major hindrance effective anticancer treatment. Extracellular vesicles (EVs) are nano-sized lipid-bilayer-enclosed particles secreted extracellular space by all cell types. They critically involved numerous biological functions including intercellular communication. Tumor-derived (TEVs) can transport variety cargo modulate cells microenvironment (TME). This review provides latest update about how evade surveillance exploiting TEVs. First, biogenesis EVs cargo-sorting machinery discussed. Second, differentiation, activation, function via TEVs illustrated. Last but not least, novel antitumor strategies reverse escape summarized.

Язык: Английский

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Tumour‐associated macrophages in gastric cancer: From function and mechanism to application

Clinical and Translational Medicine, Год журнала: 2023, Номер 13(8)

Опубликована: Авг. 1, 2023

Gastric cancer (GC) is a malignant tumour, with high morbidity and mortality rates worldwide. The occurrence development of GC complex process involving genetic changes in tumour cells the influence surrounding microenvironment (TME). Accumulative evidence shows that tumour-associated macrophages (TAMs) play vital role GC, acting as plentiful active infiltrating inflammatory TME.

Язык: Английский

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Exosome-mediated communication between gastric cancer cells and macrophages: implications for tumor microenvironment

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Фев. 22, 2024

Gastric cancer (GC) is a malignant neoplasm originating from the epithelial cells of gastric mucosa. The pathogenesis GC intricately linked to tumor microenvironment within which reside. Tumor-associated macrophages (TAMs) primarily differentiate peripheral blood monocytes and can be broadly categorized into M1 M2 subtypes. M2-type TAMs have been shown promote growth, tissue remodeling, angiogenesis. Furthermore, they actively suppress acquired immunity, leading poorer prognosis reduced tolerance chemotherapy. Exosomes, contain myriad biologically active molecules including lipids, proteins, mRNA, noncoding RNAs, emerged as key mediators communication between TAMs. exchange these via exosomes markedly influence consequently impact progression. Recent studies elucidated correlation various clinicopathological parameters GC, such size, differentiation, infiltration depth, lymph node metastasis, TNM staging, highlighting pivotal role in development metastasis. In this review, we aim comprehensively examine bidirectional TAMs, implications alterations on immune escape, invasion, metastasis targeted therapeutic approaches for efficacy potential drug resistance strategies.

Язык: Английский

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Extracellular vesicles mediated gastric cancer immune response: tumor cell death or immune escape?

Cell Death and Disease, Год журнала: 2024, Номер 15(5)

Опубликована: Май 30, 2024

Gastric cancer (GC) is a major global health issue, being the fifth most prevalent and third highest contributor to cancer-related deaths. Although treatment strategies for GC have diversified, prognosis advanced remains poor. Hence, there critical need explore new directions enhance diagnosis, treatment, patient prognosis. Extracellular vesicles (EVs) emerged as key players in tumor development progression. Different sources of EVs carry different molecules, resulting distinct biological functions. For instance, tumor-derived can promote cell proliferation, alter microenvironment immune response, while derived from cells molecules that regulate function possess tumor-killing capabilities. Numerous studies demonstrated crucial role development, escape, remodeling GC. In this review, we discuss GC-derived development. Furthermore, provide an overview potential uses immunotherapy

Язык: Английский

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The role of tumor-derived exosomal LncRNA in tumor metastasis

Cancer Gene Therapy, Год журнала: 2025, Номер unknown

Опубликована: Фев. 26, 2025

Язык: Английский

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miRNA-34a-5p Inhibits Chicken Myoblasts Proliferation and Differentiation via NOTCH1 Inhibition

Poultry Science, Год журнала: 2025, Номер 104(3), С. 104895 - 104895

Опубликована: Фев. 7, 2025

The growth performance of chickens contributes to the sustainable development broiler industry, and skeletal muscle is particularly crucial for chicken production. MicroRNAs (miRNAs) are noncoding RNAs that can participate in regulation many biological processes. MiR-34a-5p a miRNA closely related development. However, specific role miR-34a-5p remains unknown. Characteristic analysis revealed structures functions from 14 species were similar. Transmembrane domain, hydropathicity/hydrophobicity, signal peptide analyses NOTCH1 protein demonstrated may cellular life Motif identification gene structure NOTCH genes H. sapiens, M. musculus, G. gallus had similar structures, indicating they have functions. In this study, significantly inhibited primary myoblast proliferation differentiation (P < 0.05). Through miRDB TargetScan database prediction, was speculated be one target miR-34a-5p. Gene ontology enrichment Kyoto Encyclopedia Genes Genomes pathway predicted Dual-luciferase reporter, RT-qPCR, rescue experiments confirmed relationship between NOTCH1. mRNA quantitative western blot, CCK-8, EdU findings promoted analysis, Western blotting, indirect immunofluorescence myotubes summary, miRNA-34a-5p by inhibiting expression.

Язык: Английский

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The Hidden Messengers: Tumor Microenvironment-Derived Exosomal ceRNAs in Gastric Cancer Progression

Pathology - Research and Practice, Год журнала: 2025, Номер 269, С. 155905 - 155905

Опубликована: Март 9, 2025

Язык: Английский

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Glycolysis regulation in tumor‐associated macrophages: Its role in tumor development and cancer treatment

International Journal of Cancer, Год журнала: 2023, Номер 154(3), С. 412 - 424

Опубликована: Сен. 8, 2023

Tumor-associated macrophages constitute the main cell population in tumor microenvironment and play a crucial role regulating composition. Emerging evidence has revealed that metabolic profile determines tumor-associated macrophage phenotype. function is highly dependent on glucose metabolism, with glycolysis being major pathway. Recent reports have demonstrated diversity flux of complex substance communication cancer cells. However, how connects to influence progression still obscure. Moreover, while development single-cell sequencing technology allows clearer more accurate classification macrophages, profiles from perspective omics not been well summarized. Here, we review current state knowledge metabolism summarize different subtypes omics. Additionally, describe strategies targeting for therapy.

Язык: Английский

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The biological role of extracellular vesicles in gastric cancer metastasis

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Янв. 25, 2024

Gastric cancer (GC) is a tumor characterized by high incidence and mortality, with metastasis being the primary cause of poor prognosis. Extracellular vesicles (EVs) are an important intercellular communication medium. They contain bioactive substances such as proteins, nucleic acids, lipids. EVs play crucial biological role in process GC metastasis. Through mechanisms remodeling microenvironment (TME), immune suppression, promoting angiogenesis, facilitating epithelial–mesenchymal transition (EMT) mesothelial–mesenchymal (MMT), promote invasion GC. Further exploration roles will contribute to our understanding underlying may provide novel targets strategies for diagnosis treatment In this review, we summarize which influence from four aspects: TME, modulating system, influencing processes EMT MMT. Finally, briefly summarized organotropism well potential limitations

Язык: Английский

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