Linking cell mechanical memory and cancer metastasis

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(3), P. 216 - 228

Published: Jan. 18, 2024

Language: Английский

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Phenotypic Heterogeneity, Bidirectionality, Universal Cues, Plasticity, Mechanics, and the Tumor Microenvironment Drive Cancer Metastasis

Biomolecules, Journal Year: 2024, Volume and Issue: 14(2), P. 184 - 184

Published: Feb. 3, 2024

Tumor diseases become a huge problem when they embark on path that advances to malignancy, such as the process of metastasis. Cancer metastasis has been thoroughly investigated from biological perspective in past, whereas it still less explored physical perspective. Until now, intraluminal pathway cancer received most attention, while interaction cells with macrophages little attention. Apart biochemical characteristics, tumor treatments also rely microenvironment, which is recognized be immunosuppressive and, recently found, mechanically stimulates and thus alters their functions. The review article highlights other vascular metastatic route discusses impact this intercellular interplay mechanical characteristics subsequently functionality cells. For instance, can guide intravascular metastasis, whereby help circumvent adverse conditions within blood or lymphatic vessels. Macrophages induce microchannel tunneling possibly avoid forces during extra- intravasation reduce lumen due flow. key players traditional route. Moreover, effects flows are presented, influences, characterized. Finally, increased knowledge opens up new perspectives for treatment.

Language: Английский

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Biomechanics in the tumor microenvironment: from biological functions to potential clinical applications

Experimental Hematology and Oncology, Journal Year: 2025, Volume and Issue: 14(1)

Published: Jan. 11, 2025

Abstract Immune checkpoint therapies have spearheaded drug innovation over the last decade, propelling cancer treatments toward a new era of precision therapies. Nonetheless, challenges low response rates and prevalent resistance underscore imperative for deeper understanding tumor microenvironment (TME) pursuit novel targets. Recent findings revealed profound impacts biomechanical forces within on immune surveillance progression in both murine models clinical settings. Furthermore, pharmacological or genetic manipulation mechanical checkpoints, such as PIEZO1, DDR1, YAP/TAZ, TRPV4, has shown remarkable potential activation eradication tumors. In this review, we delved into underlying mechanisms resulting intricate biological meaning TME, focusing mainly extracellular matrix, stiffness cells, synapses. We also summarized methodologies employed research translation derived from current evidence. This comprehensive review biomechanics will enhance functional role provide basic knowledge discovery therapeutic

Language: Английский

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Prostate cancer cells synergistically defend against CD8⁺ T cells by secreting exosomal PD‐L1

Cancer Medicine, Journal Year: 2023, Volume and Issue: 12(15), P. 16405 - 16415

Published: July 27, 2023

Metastatic castration-resistant prostate cancer (mCRPC) remains fatal and incurable, despite a variety of treatments that can delay disease progression prolong life. Immune checkpoint therapy is promising treatment. However, emerging evidence suggests exosomal programmed necrosis ligand 1 (PD-L1) directly binds to PD-1 on the surface T cells in drain lineage lymph nodes or neutralizes administered PD-L1 antibodies, resulting poor response anti-PD-L1 mCRPC.Western blotting immunofluorescence were performed compare levels exosomes derived from different cells. PC3 subcutaneously injected into nude mice, then ELISA assay was used detect human specific purified mouse serum. The function CD8+ detected by cell mediated tumor killing FACS analysis. A subcutaneous xenograft model established using RM1, with without every 3 days, size weight analyzed evaluate effect PD-L1.Herein, we found exosomal-PD-L1 taken up expressing low PD-L1, thereby protecting them T-cell killing. Higher highly malignant DU145 lines. Moreover, PD-L1-low-expressing LNCaP line inhibited CD8-T growth rate RM1-derived tumors decreased after knockdown cells, whereas recovered following tail vein injection. Furthermore, serum mice PCa tumors, mainly present exosomes.In summary, share synergistically against through exosomes. Inhibition exosome secretion prevention sorting may improve therapeutic therapy.

Language: Английский

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Advantages of integrating Brillouin microscopy in multimodal mechanical mapping of cells and tissues

Current Opinion in Cell Biology, Journal Year: 2024, Volume and Issue: 88, P. 102341 - 102341

Published: March 11, 2024

Language: Английский

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Tissue-dependent mechanosensing by cells derived from human tumors

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Alterations of the extracellular matrix (ECM), including both mechanical (such as stiffening ECM) and chemical variation adhesion proteins deposition hyaluronic acid (HA)) changes, in malignant tissues have been shown to mediate tumor progression. To survey how cells from different tissue types respond various changes ECM mechanics composition, we measured physical characteristics (adherent area, shape, cell stiffness, speed) 25 cancer 5 non-tumorigenic lines on 7 substrate conditions. Our results indicate substantial heterogeneity within across response mechanosensitive chemosensitive ECM. The analysis also underscores role HA with some showing presence soft that are similar those observed stiff substrate. This pan-cancer investigation highlights importance tissue-type line specificity for inferences made based comparison between properties normal cells. Lastly, using unsupervised machine learning, identify phenotypic classes characterize plasticity, i.e. distribution feature values attainable, a particular type ECM-based

Language: Английский

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

Biomarker Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: March 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.

Language: Английский

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S‐Methyl Methanethiosulfonate, the Main Human Metabolite of S‐Methyl‐L‐Cysteine Sulfoxide, Alters Energy Metabolism in Prostate Cancer Cells

Molecular Nutrition & Food Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 9, 2025

Cruciferous and allium vegetables contain the sulfur compound S-methyl-L-cysteine-sulfoxide (SMCSO). Considering SMCSO is found at a higher abundance compared to glucosinolates, there are limited reports on its effect health, with majority of evidence beneficial effects glucose metabolism in rodent models. In current study, we investigated metabolic metabolite, S-methyl methanethiosulfonate (MMTSO), prostate cancer metabolism. DU145 cells were cultured 5.5 mM (basal), 10 (intermediate) 25 (high) concentrations presence or MMTSO (100 µM). Using Seahorse technology, but not reduced mitochondrial metabolism, ATP, percentage oxidative phosphorylation increased fatty acid dependency cells. Transcriptomic metabolomic analyses observed cellular energy pathways immune response changes. These data show that alters several features cells, shifting them towards non-cancerous phenotype. consistent notion may contribute broccoli-rich diet cancer.

Language: Английский

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Noninvasive holographic sensor system for measuring stiffness of soft micro samples

Journal of Biomedical Optics, Journal Year: 2025, Volume and Issue: 30(03)

Published: March 14, 2025

Significance: Measuring cell stiffness is essential in cellular biomechanics, particularly understanding disease progression, including cancer metastasis and tissue mechanics. However, conventional techniques such as atomic force microscopy optical stretching present limitations, invasiveness, low throughput, complex sample preparation. These factors restrict their applicability dynamic sensitive biological environments.Aim: This study introduces a noninvasive holographic sensor system for evaluating the of soft microscale samples.Approach: The proposed integrates imaging with acoustic stimulation using an off-axis Mach–Zehnder interferometer combined bulk waves. setup allows label-free, high-throughput measurements while preserving integrity. was validated polyacrylamide beads engineered to mimic stiffness, ensuring precise repeatable assessments.Results: Measurement errors caused by spatial variations were minimized through structured approach calibration strategy, improving uniformity across different regions. corrections enhanced consistency reliability assessments. Experimental validation demonstrated stable regardless size variations. Repeatability tests further confirmed system's robustness, producing consistent results multiple trials.Conclusion: findings highlight potential this advancing biomechanics research, diagnostics, mechanobiology. By offering noninvasive, alternative mechanical property assessments samples, method contributes improved characterization biomedical applications.

Language: Английский

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Antrodia cinnamomea Formula Suppresses Prostate Cancer Progression via Immune Modulation and PD-1/PD-L1 Pathway Inhibition

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2684 - 2684

Published: March 17, 2025

Prostate cancer remains a significant global health challenge, necessitating the development of novel therapeutic approaches. This study investigated potential Antrodia cinnamomea formula (XIANZHIFANG formula, XZF), comprising cinnamomea, Sanghuangporus sanghuang, Ganoderma lucidum, sinense, and Inonotus obliquus, in prostate treatment. HPLC analysis confirmed presence key triterpenoids, including Antcin A, B, C, K, Zhankuic acid 4,7-dimethoxy-5-methyl-1,3-benzodioxole. Cytotoxicity assays demonstrated that XZF (50–200 μg/mL) exhibited selective activity, maintaining viability non-cancerous 293T-cells while enhancing activated CD8+ CD4+ T-cells dose-dependent manner. significantly reduced PD-1 expression but not inhibited PD-L1/PD-1 interaction, achieving 93% inhibition at 200 μg/mL. Furthermore, when combined with atezolizumab (1 μg/mL), complete blockade interaction. In cells, differential antiproliferative effects. PC-3 across concentration range 25–200 μg/mL, whereas DU145 cells showed only partial higher concentrations (100–200 μg/mL). LNCaP reduction viability, mirroring response pattern cells. Conditioned medium from XZF-treated macrophages, particularly human THP-1 suppressed migration Notably, conditioned stronger inhibitory effect on cell compared to murine RAW 264.7 macrophages. These findings indicate exerts its through multiple mechanisms, direct effects enhancement T-cell responses, modulation immune checkpoint pathways, macrophage-mediated suppression survival migration. The pronounced observed macrophage models suggest promising avenue for further investigation clinical settings, combination existing immunotherapies.

Language: Английский

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