Decoding the spatiotemporal heterogeneity of tumor-associated macrophages

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: July 27, 2024

Abstract Tumor-associated macrophages (TAMs) are pivotal in cancer progression, influencing tumor growth, angiogenesis, and immune evasion. This review explores the spatial temporal heterogeneity of TAMs within microenvironment (TME), highlighting their diverse subtypes, origins, functions. Advanced technologies such as single-cell sequencing multi-omics have elucidated intricate interactions between other TME components, revealing mechanisms behind recruitment, polarization, distribution. Key findings demonstrate that support vascularization, promote epithelial-mesenchymal transition (EMT), modulate extracellular matrix (ECM) remodeling, etc., thereby enhancing invasiveness metastasis. Understanding these complex dynamics offers new therapeutic targets for disrupting TAM-mediated pathways overcoming drug resistance. underscores potential targeting to develop innovative therapies, emphasizing need further research into characteristics functional roles TME.

Language: Английский

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Navigating tumor angiogenesis: therapeutic perspectives and myeloid cell regulation mechanism

Angiogenesis, Journal Year: 2024, Volume and Issue: 27(3), P. 333 - 349

Published: April 6, 2024

Abstract Sustained angiogenesis stands as a hallmark of cancer. The intricate vascular tumor microenvironment fuels cancer progression and metastasis, fosters therapy resistance, facilitates immune evasion. Therapeutic strategies targeting vasculature have emerged transformative for treatment, encompassing anti-angiogenesis, vessel normalization, endothelial reprogramming. Growing evidence suggests the dynamic regulation by infiltrating myeloid cells, such macrophages, myeloid-derived suppressor cells (MDSCs), neutrophils. Understanding these regulatory mechanisms is pivotal in paving way successful vasculature-targeted treatments. interventions aimed to disrupt cell-mediated may reshape overcome resistance radio/chemotherapy immunotherapy.

Language: Английский

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Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 7, 2025

Abstract Macrophages are immune cells belonging to the mononuclear phagocyte system. They play crucial roles in defense, surveillance, and homeostasis. This review systematically discusses types of hematopoietic progenitors that give rise macrophages, including primitive progenitors, erythro-myeloid stem cells. These have distinct genetic backgrounds developmental processes. Accordingly, macrophages exhibit complex diverse functions body, phagocytosis clearance cellular debris, antigen presentation, response, regulation inflammation cytokine production, tissue remodeling repair, multi-level regulatory signaling pathways/crosstalk involved homeostasis physiology. Besides, tumor-associated a key component TME, exhibiting both anti-tumor pro-tumor properties. Furthermore, functional status is closely linked development various diseases, cancer, autoimmune disorders, cardiovascular disease, neurodegenerative metabolic conditions, trauma. Targeting has emerged as promising therapeutic strategy these contexts. Clinical trials macrophage-based targeted drugs, immunotherapies, nanoparticle-based therapy were comprehensively summarized. Potential challenges future directions targeting also been discussed. Overall, our highlights significance this versatile cell human health which expected inform research clinical practice.

Language: Английский

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Exosomal EPHA2 derived from highly metastatic breast cancer cells promotes angiogenesis by activating the AMPK signaling pathway through Ephrin A1-EPHA2 forward signaling

Theranostics, Journal Year: 2022, Volume and Issue: 12(9), P. 4127 - 4146

Published: Jan. 1, 2022

Rationale: Angiogenesis is a fundamental process of tumorigenesis, growth, invasion and metastatic spread.Extracellular vesicles, especially exosomes, released by primary tumors promote angiogenesis cancer progression.However, the mechanism underlying pro-angiogenic potency cell-derived exosomes remains poorly understood.Methods: Exosomes were isolated from breast cells with high potential (HM) low (LM).The effects these evaluated in vitro tube formation assays, wound healing rat arterial ring budding assays vivo Matrigel plug assays.Subsequently, RNA sequencing, shRNA-mediated gene knockdown, overexpression different EPHA2 mutants, small-molecule inhibitors used to analyze angiogenesis-promoting effect exosomal its downstream mechanism.Finally, xenograft tumor models established using expressing levels mimic secretion vivo, metastasis monitored IVIS Spectrum imaging system Computed Tomography.Results: Herein, we demonstrated that produced HM can metastasis.EPHA2 was rich HM-derived conferred effect.Exosomal be transferred endothelial cells.Moreover, it stimulate migration tube-forming abilities vivo.Mechanistically, activates AMPK signaling via ligand Ephrin A1-dependent canonical forward pathway.Moreover, inhibition impairs EPHA2-mediated effects.Conclusion: Our findings identify novel intercellular communication microenvironment provoke metastasis.Targeting EPHA2-AMPK may serve as strategy for therapy.

Language: Английский

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Bioengineered exosomal-membrane-camouflaged abiotic nanocarriers: neurodegenerative diseases, tissue engineering and regenerative medicine

Military Medical Research, Journal Year: 2023, Volume and Issue: 10(1)

Published: April 27, 2023

Abstract A bio-inspired strategy has recently been developed for camouflaging nanocarriers with biomembranes, such as natural cell membranes or subcellular structure-derived membranes. This endows cloaked nanomaterials improved interfacial properties, superior targeting, immune evasion potential, and prolonged duration of systemic circulation. Here, we summarize recent advances in the production application exosomal membrane-coated nanomaterials. The structure, manner which exosomes communicate cells are first reviewed. is followed by a discussion types their fabrication methods. We then discuss applications biomimetic membrane-cloaked tissue engineering, regenerative medicine, imaging, treatment neurodegenerative diseases. Finally, appraise current challenges associated clinical translation membrane-surface-engineered nanovehicles evaluate future this technology.

Language: Английский

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Tumor macrophage functional heterogeneity can inform the development of novel cancer therapies

Trends in Immunology, Journal Year: 2023, Volume and Issue: 44(12), P. 971 - 985

Published: Nov. 22, 2023

Macrophages represent a key component of the tumor microenvironment (TME) and are largely associated with poor prognosis. Therapeutic targeting macrophages has historically focused on inhibiting their recruitment or reprogramming phenotype from protumor (M2-like) to an antitumor (M1-like) one. Unfortunately, this approach not provided clinical breakthroughs that have changed practice. Emerging studies utilizing single-cell RNA-sequencing (scRNA-seq) spatial transcriptomics improved our understanding ontogeny, phenotype, functional plasticity macrophages. Overlaying wealth current information regarding macrophage molecular subtypes functions also identified novel therapeutic vulnerabilities might drive better control tumor-associated (TAMs). Here, we discuss profiling provide update macrophage-targeted therapies in development.

Language: Английский

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The suppression of cervical cancer ferroptosis by macrophages: The attenuation of ALOX15 in cancer cells by macrophages-derived exosomes

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 13(6), P. 2645 - 2662

Published: April 1, 2023

Induction of cancer cell ferroptosis has been proposed as a potential treatment in several types. Tumor-associated macrophages (TAMs) play key role promoting tumor malignant progression and therapy resistance. However, the roles mechanisms TAMs regulating is still unexplored remains enigmatic. This study shows inducers shown therapeutic outcomes cervical vitro vivo. have found to suppress cells ferroptosis. Mechanistically, macrophage-derived miRNA-660-5p packaged into exosomes are transported cells. In cells, attenuates ALOX15 expression inhibit Moreover, upregulation depends on autocrine IL4/IL13-activated STAT6 pathway. Importantly, clinical cases, negatively associated with infiltration, which also raises possibility that reduce levels cancer. both univariate multivariate Cox analyses show independent prognostic factor positively good prognosis Altogether, this reveals utility targeting ferroptosis-based indicators for

Language: Английский

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TRAF2 promotes M2-polarized tumor-associated macrophage infiltration, angiogenesis and cancer progression by inhibiting autophagy in clear cell renal cell carcinoma

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: July 6, 2023

The management of advanced clear cell renal carcinoma (ccRCC) remains a major challenge in clinical practice, and the construction more reliable prognostic prediction models further elucidation key molecular mechanisms tumor progression are topics urgent need in-depth investigation.We used CIBERSORT to estimate proportion 22 tumor-infiltrating immune types TCGA-KIRC cohort. Weighted gene co-expression network analysis, least absolute shrinkage selection operator regression analysis were build risk models. Expression patterns significance TRAF2 determined through bioinformatics real-time qPCR, Western Blot, immunohistochemistry. GSEA transmission electron microscopy, 2D/3D colony formation assay, migration invasion tube-formation assay investigate underlying function mechanism TRAF2/M2 macrophage/autophagy axis.We constructed novel model based on M2 macrophage-related genes, which was identified as an accurate, independent specific for ccRCC patients. A nomogram predict 1-, 3-, 5-year overall survival patients with ccRCC. As one constituent genes model, be upregulated associated poor prognosis. We found that promotes malignant by regulating macrophage polarization, angiogenesis. Mechanistically, we polarization macrophages, this chemotaxis is achieved autophagy-dependent pathway. Orthotopic growth results revealed plays role promotor metastasis.In conclusion, highly predictive patients, expected promote improved treatment evaluation comprehensive Moreover, our findings reveal axis regulatory ccRCC, suggest potential therapeutic target

Language: Английский

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The Role of Exosomes in Human Carcinogenesis and Cancer Therapy—Recent Findings from Molecular and Clinical Research

Cells, Journal Year: 2023, Volume and Issue: 12(3), P. 356 - 356

Published: Jan. 18, 2023

Exosomes are biological nanoscale spherical lipid bilayer vesicles, 40–160 nm in diameter, produced by most mammalian cells both physiological and pathological conditions. formed via the endosomal sorting complex required for transport (ESCRT). The primary function of exosomes is mediating cell-to-cell communication. In terms cancer, play important roles as mediators intercellular communication, leading to tumor progression. Moreover, they can serve biomarkers cancer detection Therefore, their utilization therapies has been suggested, either drug delivery carriers or a diagnostic tool. However, were also reported be involved resistance transferring information sensitive cells. It consider current knowledge regarding role resistance, therapies, clinical application therapies.

Language: Английский

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Omental cancer‐associated fibroblast‐derived exosomes with low microRNA‐29c‐3p promote ovarian cancer peritoneal metastasis

Cancer Science, Journal Year: 2023, Volume and Issue: 114(5), P. 1929 - 1942

Published: Jan. 16, 2023

Ovarian cancer (OC) is characterized by frequent widespread peritoneal metastasis. Cancer-associated fibroblasts (CAFs) represent a critical stromal component of metastatic niche and promote omentum metastasis in OC patients. However, the role exosomes derived from omental CAFs remains unclear. We isolated primary normal (NFs) patients (NF-Exo CAF-Exo, respectively) assessed their effect on In mice bearing orthotopic xenografts, CAF-Exo treatment led to more rapid intraperitoneal tumor dissemination shorter animal survival. Similar results were observed undergoing injection cells. Among miRNAs downregulated miR-29c-3p tissues was associated with survival Moreover, increasing significantly weakened metastasis-promoting CAF-Exo. Based RNA sequencing, expression assays, luciferase matrix metalloproteinase 2 (MMP2) identified as direct target miR-29c-3p. These verify significant contribution metastasis, which could be partially due relief MMP2 inhibition mediated low exosomal

Language: Английский

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