Exosomal cargos-mediated metabolic reprogramming in tumor microenvironment

Journal of Experimental & Clinical Cancer Research, Год журнала: 2023, Номер 42(1)

Опубликована: Март 10, 2023

Metabolic reprogramming is one of the hallmarks cancer. As nutrients are scarce in tumor microenvironment (TME), cells adopt multiple metabolic adaptations to meet their growth requirements. not only present cells, but exosomal cargos mediates intercellular communication between and non-tumor TME, inducing remodeling create an outpost microvascular enrichment immune escape. Here, we highlight composition characteristics meanwhile summarize components corresponding sorting mode. Functionally, these cargos-mediated improves "soil" for metastasis. Moreover, discuss abnormal metabolism targeted by its potential antitumor therapy. In conclusion, this review updates current role TME enriches future application scenarios exosomes.

Язык: Английский

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Extracellular vesicles and particles as mediators of long-range communication in cancer: connecting biological function to clinical applications

Extracellular Vesicles and Circulating Nucleic Acids, Год журнала: 2023, Номер 4(3), С. 461 - 485

Опубликована: Янв. 1, 2023

Over the past decade, extracellular vesicles and particles (EVPs) have emerged as critical mediators of intercellular communication, participating in numerous physiological pathological processes. In context cancer, EVPs exert local effects, such increased invasiveness, motility, reprogramming tumor stroma, well systemic including pre-metastatic niche formation, determining organotropism, promoting metastasis altering homeostasis various organs systems, liver, muscle, circulatory system. This review provides an overview advances EVP research during highlighting heterogeneity EVPs, their roles cancer progression, metastasis. Moreover, clinical potential useful biomarkers therapeutic agents is explored. Last but not least, progress analysis technologies that facilitated these discoveries discussed, which may further propel future.

Язык: Английский

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Membrane Protein Modification Modulates Big and Small Extracellular Vesicle Biodistribution and Tumorigenic Potential in Breast Cancers In Vivo

Advanced Materials, Год журнала: 2023, Номер 35(13)

Опубликована: Янв. 7, 2023

Extracellular vesicles (EVs) are released by cells to mediate intercellular communication under pathological and physiological conditions. While small EVs (sEVs; <100-200 nm, exosomes) intensely investigated, the properties functions of medium large (big (bEVs); >200 microvesicles) less well explored. Here, bEVs sEVs identified as distinct EV populations, it is determined that in a greater bEV:sEV ratio aggressive human triple-negative breast cancer (TNBC) subtype. PalmGRET, bioluminescence-resonance-energy-transfer (BRET)-based reporter, reveals dose-dependent biodistribution at nonlethal dosages, compared lipophilic fluorescent dyes. Remarkably, exhibit unique profiles, yet individually promote vivo tumor growth syngeneic immunocompetent TNBC murine model. The share mass-spectrometry-identified tumor-progression-associated surface membrane proteins (tpEVSurfMEMs), which include solute carrier family 29 member 1, Cd9, Cd44. tpEVSurfMEM depletion attenuates lung organotropism, alters biodistribution, reduces protumorigenic potential. This study identifies property function cancer, suggest significant role diseases, diagnostic therapeutic applications.

Язык: Английский

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Tumor-derived nanoseeds condition the soil for metastatic organotropism

Seminars in Cancer Biology, Год журнала: 2023, Номер 93, С. 70 - 82

Опубликована: Май 12, 2023

Язык: Английский

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Modelling the complex nature of the tumor microenvironment: 3D tumor spheroids as an evolving tool

Journal of Biomedical Science, Год журнала: 2024, Номер 31(1)

Опубликована: Янв. 23, 2024

Abstract Cancer remains a serious burden in society and while the pace development of novel more effective therapeutics is increasing, testing platforms that faithfully mimic tumor microenvironment are lacking. With clear shift from animal models to complex vitro 3D systems, spheroids emerge as strong options this regard. Years have allowed spheroid-based better reproduce biomechanical cues observed tumor-associated extracellular matrix (ECM) cellular interactions occur both cell–cell cell-ECM manner. Here, we summarize some key drive development, progression invasion, how successfully these recapitulated spheroid currently use field. We finish by speculating on future advancements field can shape relevance spherical for modelling.

Язык: Английский

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From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(17), С. 9463 - 9463

Опубликована: Авг. 30, 2024

Colorectal cancer (CRC) represents a significant global health burden, with high incidence and mortality rates worldwide. Recent progress in research highlights the distinct clinical molecular characteristics of colon versus rectal cancers, underscoring tumor location's importance treatment approaches. This article provides comprehensive review our current understanding CRC epidemiology, risk factors, pathogenesis, management strategies. We also present intricate cellular architecture colonic crypts their roles intestinal homeostasis. carcinogenesis multistep processes are described, covering conventional adenoma-carcinoma sequence, alternative serrated pathways, influential Vogelstein model, which proposes sequential

Язык: Английский

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Osteosarcoma Cell‐Derived Migrasomes Promote Macrophage M2 Polarization to Aggravate Osteosarcoma Proliferation and Metastasis

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Март 8, 2025

The local tumor microenvironment (TME) of osteosarcoma (OS) includes several niches that control growth and cell extravasation. Migrasomes are recently discovered extracellular vesicles produced during migration. Herein, the results show OS production migrasomes in vivo vitro. Osteosarcoma cell-derived (OCDMs) aggravate proliferation metastasis, impeding OCDM formation alleviates malignant progression OS. Further studies revealed migrasome-associated nanoparticles (MANPs) functional unit OCDMs promote M2 polarization macrophages TME a MANPs-dependent manner. Moreover, milk fat globule-EGF factor 8 (MFGE8) is identified as key protein enhances phagocytosis to macrophages. Overall, reveal enhance via MFGE8. These findings may guide development OCDM-modulating therapies.

Язык: Английский

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TGFβ⁺ small extracellular vesicles from head and neck squamous cell carcinoma cells reprogram macrophages towards a pro‐angiogenic phenotype

Journal of Extracellular Vesicles, Год журнала: 2022, Номер 11(12)

Опубликована: Дек. 1, 2022

Abstract Transforming growth factor β (TGFβ) is a major component of tumor‐derived small extracellular vesicles (TEX) in cancer patients. Mechanisms utilized by TGFβ + TEX to promote tumor and pro‐tumor activities the microenvironment (TME) are largely unknown. produced head neck squamous cell carcinoma (HNSCC) lines carried angiogenesis‐promoting proteins. stimulated macrophage chemotaxis without notable M1/M2 phenotype shift reprogrammed primary human macrophages pro‐angiogenic characterized upregulation factors functions. In murine basement membrane extract plug model, promoted infiltration vascularization ( p < 0.001), which was blocked using ligand trap mRER 0.001). injected into mice undergoing 4‐nitroquinoline‐1‐oxide (4‐NQO)‐driven oral carcinogenesis angiogenesis 0.05), M2‐like TME 0.05) ultimately progression 0.05). Inhibition signaling with ameliorated these activities. Silencing emerges as critical step suppressing functions HNSCC.

Язык: Английский

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Weaving the nest: extracellular matrix roles in pre-metastatic niche formation

Frontiers in Oncology, Год журнала: 2023, Номер 13

Опубликована: Июнь 7, 2023

The discovery that primary tumors condition distant organ sites of future metastasis for seeding by disseminating tumor cells through a process described as the pre-metastatic niche (PMN) formation revolutionized our understanding cancer progression and opened new avenues therapeutic interventions. Given inherent inefficiency metastasis, PMN generation is crucial to ensure survival rare in otherwise hostile environments metastatic organs. Early on, it was recognized preparing "soil" distal support outgrowth initiating event development, achieved remodeling organ's extracellular matrix (ECM). Remote restructuring ECM at under influence tumor-secreted factors an iterative orchestrated crosstalk between resident stromal cells, such fibroblasts, epithelial endothelial recruited innate immune cells. In this review, we will explore changes, cellular effectors, mechanisms throughout progression, well its impact on shaping ultimately promoting metastasis. Moreover, highlight clinical translational implications changes opportunities therapeutically targeting hinder formation.

Язык: Английский

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Proteomic analysis of ascitic extracellular vesicles describes tumour microenvironment and predicts patient survival in ovarian cancer

Journal of Extracellular Vesicles, Год журнала: 2024, Номер 13(3)

Опубликована: Март 1, 2024

High-grade serous carcinoma of the ovary, fallopian tube and peritoneum (HGSC), most common type ovarian cancer, ranks among deadliest malignancies. Many HGSC patients have excess fluid in called ascites. Ascites is a tumour microenvironment (TME) containing various cells, proteins extracellular vesicles (EVs). We isolated EVs from patients' ascites by orthogonal methods analyzed them mass spectrometry. identified not only set 'core ascitic EV-associated proteins' but also defined their subset unique to Using single-cell RNA sequencing data, we mapped origin HGSC-specific different types cells present Surprisingly, did come predominantly non-malignant cell such as macrophages fibroblasts. Flow cytometry combination with analysis EV protein composition matched samples showed that type-specific markers has more substantial prognostic potential than cells. To conclude, provide evidence proteomic can define cellular TME. This finding opens numerous avenues both for better understanding EV's role promotion/prevention improved diagnostics.

Язык: Английский

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