Exposure of benzo[a]pyrene induces HCC exosome‐circular RNA to activate lung fibroblasts and trigger organotropic metastasis

Cancer Communications, Год журнала: 2024, Номер 44(7), С. 718 - 738

Опубликована: Июнь 5, 2024

Abstract Background Benzo[a]pyrene (B[a]P), a carcinogen pollutant produced by combustion processes, is present in the western diet with grilled meats. Chronic exposure of B[a]P hepatocellular carcinoma (HCC) cells promotes metastasis rather than primary proliferation, implying an unknown mechanism B[a]P‐induced malignancy. Given that exosomes carry bioactive molecules to distant sites, we investigated whether and how mediate cancer‐stroma communications for toxicologically associated microenvironment. Method Exosomes were isolated from stimulated BEL7404 HCC (7404‐100Bap Exo) at environmental relevant dose (100 nmol/L). Lung pre‐education animal model was prepared via injection cytokines. The inflammatory genes educated lungs evaluated using quantitative reverse transcription PCR array. LM3 transfected firefly luciferase next injected monitor tumor burdens organotropic metastasis. Profile B[a]P‐exposed determined ceRNA microarray. Interactions between circular RNA (circRNA) microRNAs (miRNAs) detected pull‐down target lung fibroblasts. Fluorescence situ hybridization immunoprecipitation assay used evaluate “on‐off” interaction circRNA‐miRNA pairs. We further developed adeno‐associated virus inhalation examine mRNA expression specific lung, thereby exploring targets induced cascade. Results fibroblasts exert activation phenotypes, including focal adhesion motility altered 7404‐100Bap Exo. In exosome‐educated vivo model, fibrosis factors pro‐inflammatory are up‐regulated when exosomes. Compared non‐exposed 7404 cells, circ_0011496 following treatment mainly packaged into Exosomal delivered competitively bound miR‐486‐5p recipient down‐regulation converted fibroblast cancer‐associated regulating downstream Twinfilin‐1 (TWF1) matrix metalloproteinase‐9 (MMP9) Additionally, increased TWF1, specifically exosomal lungs, could promote crosstalk activating vascular endothelial growth factor (VEGF). These modulated promoted angiogenesis recruited invasion, as consequence pre‐metastatic niche formation. Conclusion demonstrated can deliver activate miR‐486‐5p/TWF1/MMP9 cascade fibroblasts, generating feedback loop

Язык: Английский

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Pollutants in Microenvironmental Cellular Interactions During Liver Inflammation Cancer Transition and the Application of Multi-Omics Analysis

Toxics, Год журнала: 2025, Номер 13(3), С. 163 - 163

Опубликована: Фев. 25, 2025

This study categorizes pollutant-induced inflammation–cancer transition into three stages: non-alcoholic fatty liver disease (NAFLD), fibrosis, and hepatocellular carcinoma (HCC). It systematically reveals the temporal heterogeneity of damage. The findings indicate that pollutants not only directly damage hepatocytes but also modulate key cells in immune microenvironment, such as hepatic stellate (HSCs) Kupffer cells, thereby amplifying inflammatory fibrotic responses, ultimately accelerating progression HCC. Mechanistically, early stage primarily cause hepatocyte injury through oxidative stress lipid metabolism dysregulation. During fibrosis stage, promote by inducing extracellular matrix accumulation, while HCC they drive tumorigenesis via activation Wnt/β-catenin pathway p53 inactivation. Through multi-omics analyses, this identifies critical pathogenic molecules signaling pathways regulated pollutants, providing new insights their mechanisms, potential biomarkers, therapeutic targets. These offer valuable guidance for development diagnostic strategies diseases formulation environmental health risk prevention measures.

Язык: Английский

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Focal adhesion in the tumour metastasis: from molecular mechanisms to therapeutic targets

Biomarker Research, Год журнала: 2025, Номер 13(1)

Опубликована: Март 5, 2025

The tumour microenvironment is the "hotbed" of cells, providing abundant extracellular support for growth and metastasis. However, not static constantly remodelled by a variety cellular components, including through mechanical, biological chemical means to promote Focal adhesion plays an important role in cell-extracellular matrix adhesion. An in-depth exploration focal metastasis, especially their contribution at biomechanical level, direction current research. In this review, we first summarize assembly adhesions explore kinetics cells. Then, describe detail various stages its key functions cell migration, invasion, remodelling. Finally, anti-tumour strategies targeting progress development some inhibitors against proteins. paper, time that play positive feedback pro-tumour metastatic remodelling summarizing five processes multidimensional way. It beneficial researchers have deeper understanding behaviour metastasis potential as therapeutic target, new ideas prevention treatment metastases.

Язык: Английский

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Advances in the roles and molecular mechanisms of exosomal circular RNAs in regulating the pre-metastatic niche of tumors

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 19, 2025

Metastasis remains a major cause of morbidity and mortality in patients with malignant tumors. The pre-metastatic niche is prerequisite for distant metastasis driven by primary Circular RNAs (circRNAs), class single-stranded closed non-coding RNAs, exhibit high stability, evolutionary conservation, cell-type specificity. Exosomes, as natural carriers circRNAs, mediate intercellular communication contribute to the formation niche; however, mechanisms which they do so remain incompletely understood. This review summarizes biological characteristics functions exosomal circRNAs outlines molecular pathways through shape tumor microenvironment, emphasis on immunosuppression, vascular permeability, extracellular matrix remodeling, lymphangiogenesis. first focus functional roles regulation, providing basis development therapeutic strategies targeting metastatic progression.

Язык: Английский

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Emerging roles of exosomal circRNAs in non-small cell lung cancer

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 30, 2025

Despite the prevalence of non-small cell lung cancer (NSCLC) is high, limited early detection and management these tumors are restricted since there an absence reliable precise diagnostic biomarkers therapeutic targets. Exosomes transport functional molecules for facilitating intercellular communication, especially in tumor microenvironment, indicating their potential as Circular RNA (circRNA), a type non-coding possessing covalently closed loop structure, substantial abundance, tissue-specific expression patterns, stably enriched exosomes. In recent years, significant breakthroughs have been made research on exosomal circRNA NSCLC. This review briefly introduces biogenesis, characterizations, functions circRNAs exosomes, systematically describes biological mechanisms addition, this study summarizes role progression NSCLC discusses clinical significance targets

Язык: Английский

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Case Report: FAP+ fibroblasts and SPP1+ macrophages in SMARCA2-deficient while SMARCA4-preserved poorly differentiated lung adenocarcinoma: two case reports and multi-omics analysis

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Май 16, 2025

Two ATPase subunits, SMARCA4 (which encodes BRG1) and SMARCA2 BRM), facilitate this process by hydrolyzing ATP to energize the activity of mammalian switch/sucrose-non-fermenting (mSWI/SNF) complexes. Clinically, SMARCA4-deficient non-small cell lung carcinoma (SMARCA4-dNSCLC) were associated with poorly differentiated histologic manifestations poor prognosis. However, NSCLC exhibited similar features but loss retained have so far been underrecognized. Here, we reported two cases tumors expression while preserved provided morphologic, immunohistochemical, genetic characterization these tumors, which both arose in elderly male appeared as pulmonary lesion. Furthermore, perform a comprehensive multi-omics analysis transcriptomic cohort GSE31210 (n=226), proteomic from study Chen et al. (n=89), multiplexed immunohistochemistry (IHC) staining decipher prognosis dependent on immunosuppressive barrier formed FAP + fibroblasts SPP1 macrophages SMARCA2-deficient SMARCA4-preserved adenocarcinoma (LUAD). The report provides novel insights into distinct roles LUAD pathogenesis, highlighting tumor microenvironment deficiency.

Язык: Английский

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Animal models of lung cancer: Phenotypic comparison of different animal models of lung cancer and their application in the study of mechanisms

Animal Models and Experimental Medicine, Год журнала: 2025, Номер unknown

Опубликована: Май 19, 2025

Abstract Lung cancer has one of the highest rates incidence and mortality worldwide, making research on its mechanisms treatments crucial. Animal models are essential in lung as they accurately replicate biological characteristics treatment outcomes seen human diseases. Currently, various have been established, including chemical induction models, orthotopic transplantation ectopic metastasis gene editing mouse models. Additionally, grafts can be categorized into two types: tissue‐based cell‐based grafts. This paper summarizes phenotypes, advantages, disadvantages methods based their modeling techniques. The goal is to enhance simulation clinical establish a solid foundation for future research.

Язык: Английский

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Biological functions and molecular mechanisms of circHIPK3 in digestive system tumors

Human Cell, Год журнала: 2025, Номер 38(4)

Опубликована: Май 29, 2025

Язык: Английский

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Global hotspots and trends in pre-metastatic niche research: a bibliometric analysis(2005-2024)

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Май 29, 2025

Background The pre-metastatic niche (PMN) represents the microenvironment established in target organs before primary tumor metastasis, playing a crucial role organ-specific metastasis. Understanding and preventing PMN formation holds promise for enhancing immunotherapy efficacy reducing cancer-related mortality. Despite significance of this field, comprehensive bibliometric analysis is lacking. This study aims to identify global research trends hotspots through systematic evaluation, providing foundation future advancements field. Methods Publications related from 2005 2024 were retrieved Web Science Core Collection database. Bibliometric analyses visualizations conducted using VOSviewer, CiteSpace, Microsoft Excel, ArcGIS, Scimago Graphica, Charticulator. Results included 1,303 publications authored by 7,955 researchers 1,627 institutions across 62 countries, with articles published 400 journals. China United States emerged as central contributors research. has led publication volume institutional representation, while produced most high-quality papers impactful authors. Cancers PMN-related papers, Cancer Research had citations co-citations. Professor David Lyden Cornell University, USA, was identified influential scholar Analysis references keywords suggests will focus on metastatic organotropism, extracellular vesicles, innate immunocytes (e.g., macrophages neutrophils), immunotherapy. Conclusion first scientific output over past two decades. By summarizing current status identifying provides valuable insights reference point aiming prevent treat metastasis effectively.

Язык: Английский

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Targeted Lung Premetastasis Niche: Mechanisms, Strategies, and Application

MedComm, Год журнала: 2025, Номер 6(6)

Опубликована: Июнь 1, 2025

ABSTRACT Lung metastasis remains a leading cause of cancer mortality, driven not only by primary tumors but crucially dynamic interactions within the premetastatic niche (PMN). Emerging evidence reveals that organ‐specific PMN formation precedes tumor cell arrival, creating an immunosuppressive microenvironment conducive to metastatic colonization. Primary tumor‐derived factors interact with lung resident cells, promoting recruitment bone marrow‐derived cells and favorable for migrating cells. Despite progress, systematic integration PMN's multilayered regulatory mechanisms—from mechanism clinical application lacking. The review summarizes recent studies investigating effects in entire process metastasis. Our discussion revolves primarily around extracellular vesicles, matrix remodeling, proinflammation, immunosuppression, angiogenesis, metabolic reprogramming. We emphasize impact various treatment strategies on practice, while also summarizing current diagnostic methods exploring new therapeutic possibilities PMN. Finally, we propose roadmap future investigations into PMN, highlighting prioritized research axes bridge mechanistic discoveries bench‐to‐bedside translation PMN‐targeted interventions.

Язык: Английский

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