Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 2, 2024

Abstract Metastasis remains a pivotal characteristic of cancer and is the primary contributor to cancer-associated mortality. Despite its significance, mechanisms governing metastasis are not fully elucidated. Contemporary findings in domain biology have shed light on molecular aspects this intricate process. Tumor cells undergoing invasion engage with other cellular entities proteins en route their destination. Insights into these engagements enhanced our comprehension principles directing movement adaptability metastatic cells. The tumor microenvironment plays role facilitating proliferation by enabling navigate through stromal barriers. Such attributes influenced genetic epigenetic changes occurring surrounding milieu. A profound understanding process’s biological indispensable for devising efficacious therapeutic strategies. This review delves recent developments concerning metastasis-associated genes, important signaling pathways, microenvironment, metabolic processes, peripheral immunity, mechanical forces metastasis. In addition, we combine advances particular emphasis prospect developing effective interventions including most popular immunotherapies nanotechnology combat We also identified limitations current research metastasis, encompassing drug resistance, restricted animal models, inadequate biomarkers early detection methods, as well heterogeneity among others. It anticipated that comprehensive will significantly contribute advancement research.

Language: Английский

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TREM2 deficiency aggravates renal injury by promoting macrophage apoptosis and polarization via the JAK-STAT pathway in mice

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(6)

Published: June 7, 2024

Abstract The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune that affects cellular phenotypes by modulating phagocytosis and metabolism, promoting cell survival, counteracting inflammation. Its role in renal injury, particular, unilateral ureteral obstruction (UUO) or ischemia-reperfusion injury (IRI)-induced remains unclear. In our study, WT Trem2 −/− mice were employed to evaluate the of TREM2 macrophage infiltration tissue after UUO. Bone marrow-derived macrophages (BMDM) from both mouse genotypes cultured polarized for vitro experiments. Next, effects polarization IRI also explored. We found expression was upregulated obstructed kidneys. deficiency exacerbated inflammation fibrosis 3 7 days UUO, association with reduced infiltration. BMDM exhibited increased apoptosis poorer survival compared BMDM. Meanwhile, augmented M1 M2 Consistent vivo observations, led towards proinflammatory phenotype. Mechanistically, promoted via JAK-STAT pathway presence TGF-β1, thereby affecting regulating mTOR signaling. Furthermore, cyclocreatine supplementation alleviated death caused deficiency. Additionally, we fibrosis, mice. current data suggest aggravates pathway. These findings have implications regulation justify further evaluation.

Language: Английский

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Gold Nanoparticles Modulate Macrophage Polarization to Promote Skeletal Muscle Regeneration

Materials Today Bio, Journal Year: 2025, Volume and Issue: 32, P. 101653 - 101653

Published: March 12, 2025

Skeletal muscle regeneration is a complex process that depends on the interplay between immune responses and stem cell (MuSC) activity. Macrophages play crucial role in this process, exhibiting distinct polarization states-M1 (pro-inflammatory) M2 (anti-inflammatory)-that significantly affect tissue repair outcomes. Recent advancements nanomedicine have positioned gold nanoparticles (Au NPs) as promising tools for modulating macrophage enhancing regeneration. This review examines of Au NPs influencing behavior, focusing their physicochemical properties, biocompatibility, mechanisms action. We discuss how can promote polarization, facilitating through modulation cytokine production, interaction with surface receptors, activation intracellular signaling pathways. Additionally, we highlight benefits MuSC function, angiogenesis, extracellular matrix remodeling. Despite potential skeletal regeneration, challenges remain optimizing nanoparticle design, developing targeted delivery systems, understanding long-term effects. Future directions should focus personalized medicine approaches combination therapies to enhance therapeutic efficacy. Ultimately, emphasizes transformative regenerative medicine, offering hope improved treatments injuries diseases.

Language: Английский

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Nanomaterials modulate tumor-associated macrophages for the treatment of digestive system tumors

Bioactive Materials, Journal Year: 2024, Volume and Issue: 36, P. 376 - 412

Published: March 21, 2024

The treatment of digestive system tumors presents challenges, particularly in immunotherapy, owing to the advanced immune tolerance system. Nanomaterials have emerged as a promising approach for addressing these challenges. They provide targeted drug delivery, enhanced permeability, high bioavailability, and low toxicity. Additionally, nanomaterials target immunosuppressive cells reshape tumor microenvironment (TIME). Among various TIME, tumor-associated macrophages (TAMs) are most abundant play crucial role progression. Therefore, investigating modulation TAMs by is great significance. Here, we present comprehensive review utilization modulate gastric cancer, colorectal hepatocellular carcinoma, pancreatic cancer. We also investigated underlying mechanisms which treat Furthermore, this summarizes macrophage-derived tumors. Overall, research offers valuable insights into development tailored

Language: Английский

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The Pivotal Role of Macrophages in the Pathogenesis of Pancreatic Diseases

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5765 - 5765

Published: May 25, 2024

The pancreas is an organ with both exocrine and endocrine functions, comprising a highly organized complex tissue microenvironment composed of diverse cellular non-cellular components. impairment microenvironmental homeostasis, mediated by the dysregulation cell-to-cell crosstalk, can lead to pancreatic diseases such as pancreatitis, diabetes, cancer. Macrophages, key immune effector cells, dynamically modulate their polarization status between pro-inflammatory (M1) anti-inflammatory (M2) modes, critically influencing homeostasis thus playing pivotal role in pathogenesis disease. This review aims summarize current findings provide detailed mechanistic insights into how alterations macrophage contribute disorders. By analyzing research comprehensively, this article endeavors deepen our understanding regulatory molecules that affect polarity intricate crosstalk regulates function within microenvironment, thereby facilitating development innovative therapeutic strategies target perturbations microenvironment.

Language: Английский

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Breaking the stromal barrier in pancreatic cancer: Advances and challenges

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2023, Volume and Issue: 1879(1), P. 189065 - 189065

Published: Dec. 30, 2023

Language: Английский

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Qijiao Shengbai Capsule alleviated leukopenia by interfering leukotriene pathway: Integrated network study of multi-omics

Phytomedicine, Journal Year: 2024, Volume and Issue: 128, P. 155424 - 155424

Published: Feb. 7, 2024

Language: Английский

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Bioinformatic analysis of ferroptosis related biomarkers and potential therapeutic targets in vitiligo

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 15, 2025

Vitiligo is a complex autoimmune skin disorder characterized by depigmentation and immune dysregulation. To elucidate the role of ferroptosis-related genes (FRGs) in vitiligo, we conducted comprehensive analysis gene expression data from GSE53146 GSE65127 datasets obtained GEO database. We identified 31 differentially expressed FRGs (DE-FRGs), with 21 upregulated 10 downregulated. Functional enrichment revealed that these DE-FRGs are significantly involved oxidative stress, regulation, vitiligo-associated signaling pathways. Utilizing machine learning approaches, including LASSO SVM-RFE, four key marker (ALOX5, SNCA, SLC1A4, IL33) strong diagnostic potential. Immune landscape demonstrated influence cell composition, particularly showing correlations CD8 + T cells regulatory cells. Furthermore, drug-gene interaction proposed potential therapeutic targets, while ceRNA network uncovered intricate relationships involving miRNAs lncRNAs. Collectively, our findings provide novel insights into molecular mechanisms underpinning vitiligo suggest new avenues for development.

Language: Английский

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The role of macrophages in liver metastasis: mechanisms and therapeutic prospects

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 17, 2025

Metastasis is a hallmark of advanced cancer, and the liver common site for secondary metastasis many tumor cells, including colorectal, pancreatic, gastric, prostate cancers. Macrophages in microenvironment (TME) promote cell through various mechanisms, angiogenesis immunosuppression, play unique role development metastasis. are affected by variety factors. Under conditions hypoxia increased acidity TME, more factors now found to polarization macrophages M2 type, exosomes amino acids. M2-type secretion such as VEGF, IL-1β, TGF-β1. subjected multiple regulatory mechanisms. They also interact with cells within co-regulate certain conditions, creation an immunosuppressive microenvironment. This interaction promotes metastasis, drug resistance, immune escape. Based on advent single-cell sequencing technology, further insights into macrophage subpopulations may help exploring new therapeutic targets future. In this paper, we will focus how affect well other each other, investigate mechanisms involved their potential targets.

Language: Английский

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Identification of prognostic and therapeutic biomarkers associated with macrophage and lipid metabolism in pancreatic cancer

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 25, 2025

Although macrophages and lipid metabolism significantly influence the progression of various cancers, their precise roles in pancreatic cancer (PC) remain unclear. This study focuses on identifying validating biomarkers associated with macrophage-related genes (MRGs) metabolism-related (LMRGs), providing new targets strategies for therapeutic intervention. research utilized datasets from TCGA-PAAD, GSE62452, GSE57495. Candidate were identified by overlapping differentially expressed MRGs WGCNA LMRGs. Regression analyses performed to pinpoint potential construct a risk model, which underwent evaluation. A nomogram was subsequently developed validated. Additional analyses, including functional enrichment, somatic mutation profiling, immune landscape assessment, RT-qPCR, investigate underlying biological mechanisms PC. The ADH1A, ACACB, CD36, CERS4, PDE3B, ALOX5, CRAT as RT-qPCR results revealed reduced expression tumor samples compared adjacent tissues, whereas ALOX5 elevated samples. model utilizing these classified PC patients into high- low-risk cohorts, high-risk showing lower survival probabilities. Subsequently, score N stage independent prognostic factors, leading development nomogram. Notably, both cohorts showed significant enrichment "cell cycle" pathway. Furthermore, TP53 mutations prevalent (76%) (50%) cohorts. Correlation analysis indicated that PVRL2 (an immunosuppressive factor), CD276 immunoactivator), CCL20 (a chemotactic factor) had highest positive correlation score. In this study, PC, levels validated clinical These findings offered theoretical foundation developing targeted treatments

Language: Английский

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