Multi-stage mechanisms of tumor metastasis and therapeutic strategies

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 11, 2024

The cascade of metastasis in tumor cells, exhibiting organ-specific tendencies, may occur at numerous phases the disease and progress under intense evolutionary pressures. Organ-specific relies on formation pre-metastatic niche (PMN), with diverse cell types complex interactions contributing to this concept, adding a new dimension traditional cascade. Prior metastatic dissemination, as orchestrators PMN formation, primary tumor-derived extracellular vesicles prepare fertile microenvironment for settlement colonization circulating cells distant secondary sites, significantly impacting cancer progression outcomes. Obviously, solely intervening sites passively after macrometastasis is often insufficient. Early prediction holistic, macro-level control represent future directions therapy. This review emphasizes dynamic intricate systematic alterations that progresses, illustrates immunological landscape creation, deepens understanding treatment modalities pertinent metastasis, thereby identifying some prognostic predictive biomarkers favorable early predict occurrence design appropriate combinations.

Язык: Английский

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Pre-metastatic niche: formation, characteristics and therapeutic implication

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Сен. 25, 2024

Язык: Английский

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The role of extracellular vesicles in circulating tumor cell-mediated distant metastasis

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Ноя. 30, 2023

Current research has demonstrated that extracellular vesicles (EVs) and circulating tumor cells (CTCs) are very closely related in the process of distant metastasis. Primary tumors shed released into bloodstream to form CTCs referred as seeds colonize grow soil-like target organs, while EVs nontumor origin act fertilizers There is no previous text provides a comprehensive review role on during In this paper, we reviewed mechanisms metastasis, including ability enhance shedding CTCs, protect circulation determine direction CTC thus affecting metastasis tumors.

Язык: Английский

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Bone-targeting exosome nanoparticles activate Keap1 / Nrf2 / GPX4 signaling pathway to induce ferroptosis in osteosarcoma cells

Journal of Nanobiotechnology, Год журнала: 2023, Номер 21(1)

Опубликована: Сен. 30, 2023

In recent years, the development of BMSCs-derived exosomes (EXO) for treatment osteosarcoma (OS) is a safe and promising modality OS treatment, which can effectively deliver drugs to tumor cells in vivo. However, differences carried, binding EXOs other organs limit their therapeutic efficacy. Therefore, improving OS-targeting ability BMSCs developing new crucial clinical application targeted therapy OS.In this study, we constructed potential nano platform by modifying using bone-targeting peptide SDSSD encapsulated capreomycin (CAP) within shell. These nanoparticles (NPs) showed homologous targeting (BT-EXO) significantly promotes cellular endocytosis vitro accumulation Furthermore, our results revealed that NPs induced ferroptosis prompting excessive reactive oxygen species (ROS), Fe2+ aggregation, lipid peroxidation further identified anticancer molecular mechanism as transduced Keap1/Nrf2/GPX4 signaling pathway. Also, these NP-directed significant inhibition growth vivo with no side effects.These suggest have superior activity mouse models vivo, providing strategy combining ferroptosis-based chemotherapy OS.

Язык: Английский

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Genetically engineered loaded extracellular vesicles for drug delivery

Trends in Pharmacological Sciences, Год журнала: 2024, Номер 45(4), С. 350 - 365

Опубликована: Март 19, 2024

Язык: Английский

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Strategies for labelling of exogenous and endogenous extracellular vesicles and their application for in vitro and in vivo functional studies

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Март 9, 2024

Abstract This review presents a comprehensive overview of labelling strategies for endogenous and exogenous extracellular vesicles, that can be utilised both in vitro vivo. It covers broad spectrum approaches, including fluorescent bioluminescent labelling, provides an analysis their applications, strengths, limitations. Furthermore, this article techniques use radioactive tracers contrast agents with the ability to track EVs spatially temporally. Emphasis is also placed on mechanisms, represented by Cre-lox CRISPR-Cas systems, which are powerful flexible tools real-time EV monitoring or tracking fate target cells. By summarizing latest developments across these diverse techniques, researchers reference select most appropriate method based research.

Язык: Английский

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The capture of extracellular vesicles endogenously released by xenotransplanted tumours induces an inflammatory reaction in the premetastatic niche

Journal of Extracellular Vesicles, Год журнала: 2023, Номер 12(5)

Опубликована: Май 1, 2023

Abstract The capture of tumour‐derived extracellular vesicles (TEVs) by cells in the tumour microenvironment (TME) contributes to metastasis and notably formation pre‐metastatic niche (PMN). However, due challenges associated with modelling release small EVs vivo, kinetics PMN response endogenously released TEVs have not been examined. Here, we studied endogenous mice orthotopically implanted metastatic human melanoma (MEL) neuroblastoma (NB) releasing GFP‐tagged (GFTEVs) their host demonstrate active contribution metastasis. Human GFTEVs captured mouse macrophages vitro resulted transfer GFP exosomal miR‐1246. Mice MEL or NB showed presence blood between 5 28 days after implantation. Moreover, kinetic analysis TEV resident relative arrival outgrowth TEV‐producing organs demonstrated that lung liver precedes homing cells, consistent critical roles formation. Importantly, at future sites was miR‐1246 macrophages, stellate cells. This is first demonstration organotropic as TEV‐capturing only absence non‐metastatic organs. induced dynamic changes inflammatory gene expression which evolved a pro‐tumorigenic reaction progressed state. Thus, our work describes novel approach tracking vivo provides additional insights into role earliest stages progression.

Язык: Английский

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Small extracellular vesicles and particles (sEVPs) derived from tumor-free pre-metastatic organs promote breast cancer metastasis and support organotropism

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Март 8, 2025

Metastatic breast cancer remains largely incurable, partly due to our incomplete understanding of its intricate underlying mechanisms. Notably, intercellular communication mediated by small extracellular vesicles and particles (sEVPs) has emerged as a key feature metastasis. While tumor-derived sEVPs have been extensively studied are known be pro-metastatic, the role from metastasis-prone normal tissue sites primarily undefined. Here, we characterized function secreted tumor-free pre-metastatic organs (TuFMO-sEVPs) such brain lungs in both immunocompetent patient-derived xenograft models. TuFMO-sEVPs mammary tumor-bearing mice were found distinct protein content compared brain-sEVPs mice, suggesting that primary tumor can systemically influence cargo TuFMO-sEVPs. Importantly, orthotopically injected with cells which had educated either or lung prior transplantation showed significantly increased metastasis respective organ. We further demonstrated induced expression enzyme dihydrofolate reductase (DHFR) upon uptake cells, leading their enhanced metastatic capacity. Organ-specific signatures generated TuFMO-sEVP samples patients these also correlated poorer patient outcome. Collectively, data reveals novel facet cascade, implicating for directing providing potential therapeutic strategy targeting this process.

Язык: Английский

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Targeting the myeloid microenvironment in neuroblastoma

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

Опубликована: Дек. 13, 2023

Abstract Myeloid cells (granulocytes and monocytes/macrophages) play an important role in neuroblastoma. By inducing a complex immunosuppressive network, myeloid pose challenge for the adaptive immune system to eliminate tumor cells, especially high-risk This review first summarizes pro- anti-tumorigenic functions of including granulocytes, monocytes, macrophages, myeloid-derived suppressor (MDSC) during development progression Secondly, we discuss how are engaged current treatment regimen explore novel strategies target these These include: (1) engaging as effector (2) ablating or blocking recruitment microenvironment (3) reprogramming cells. Here describe that despite their traits, tumor-associated can still be which is clear anti-GD2 immunotherapy. However, full potential not yet reached, cell engagement enhanced, example by targeting CD47/SIRPα axis. Though depletion infiltration has been proven effective, this strategy also depletes possible immunotherapy from microenvironment. Therefore, suppressive might optimal strategy, reverses preserves effectors immunotherapy, subsequently reactivates tumor-infiltrating T

Язык: Английский

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Recent advances to address challenges in extracellular vesicle-based applications for lung cancer

Acta Pharmaceutica Sinica B, Год журнала: 2024, Номер 14(9), С. 3855 - 3875

Опубликована: Июнь 20, 2024

Lung cancer, highly prevalent and the leading cause of cancer-related death globally, persists as a significant challenge due to lack definitive tumor markers for early diagnosis personalized therapeutic interventions. Recently, extracellular vesicles (EVs), functioning natural carriers intercellular communication, have received increasing attention their ability traverse biological barriers deliver diverse cargoes, including cytosolic proteins, cell surface microRNA, lncRNA, circRNA, DNA, lipids. EVs are increasingly recognized valuable resource non-invasive liquid biopsy, well drug delivery platforms, anticancer vaccines precision medicine in lung cancer. Herein, given diagnostic potential tumor-associated we discuss this topic from translational standpoint. We delve into specific roles that play cancer carcinogenesis offer particular perspective on how advanced engineering technologies can overcome current challenges expedite and/or enhance translation laboratory research clinical settings.

Язык: Английский

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