Elastic properties of leukemic cells linked to maturation stage and integrin activation DOI Creative Commons
Ceri J. Richards,

Albertus T.J. Wierenga,

Annet Z. Brouwers-Vos

и другие.

iScience, Год журнала: 2025, Номер 28(4), С. 112150 - 112150

Опубликована: Март 4, 2025

Acute myeloid leukemia (AML) remains challenging to cure. In addition mutations that alter cell functioning, biophysical properties are modulated by external cues. particular, membrane proteins interact with the bone marrow niche can induce cellular changes. Here, we develop an atomic force microscopy (AFM) approach measure non-adherent AML mechanical properties. The Young's modulus of line, THP-1, increased in response retronectin, whereas knock-out adhesion protein ITGB1 resulted no retronectin. Confocal revealed different actin cytoskeleton morphologies for wild-type and cells exposed These results indicate mediates stimuli-induced mechanoresponses through cytoskeletal We next used AFM investigate elastic primary found more committed had lower moduli than immature AMLs. Overall, this provides a platform investigating molecular mechanisms involved leukemic mechanoresponse.

Язык: Английский

Bioactivity evaluation of Polygonum minus and identification of synergistic phytochemicals with 5-fluorouracil for colon cancer treatment DOI
Zhongming Yang, Zhongguo Yang, Md Zuki Abu Bakar

и другие.

Microchemical Journal, Год журнала: 2025, Номер 210, С. 112917 - 112917

Опубликована: Янв. 30, 2025

Язык: Английский

Процитировано

2
Mechanical signatures in cancer metastasis DOI Creative Commons
Ayushi Agrawal,

Yousef Javanmardi,

Sara A. Watson

и другие.

npj Biological Physics and Mechanics., Год журнала: 2025, Номер 2(1)

Опубликована: Фев. 4, 2025

Abstract The cancer metastatic cascade includes a series of mechanical barrier-crossing events, involving the physical movement cells from their primary location to distant organ. This review describes changes that influence tumour proliferation, progression, and metastasis. We identify potential signatures at every step discuss some latest mechanobiology-based therapeutic interventions highlight importance interdisciplinary approaches in diagnosis treatment.

Язык: Английский

Процитировано

2
Compressive stresses in cancer: characterization and implications for tumour progression and treatment DOI

Julia A Linke,

Lance L. Munn, Rakesh K. Jain

и другие.

Nature reviews. Cancer, Год журнала: 2024, Номер 24(11), С. 768 - 791

Опубликована: Окт. 10, 2024

Язык: Английский

Процитировано

10
Engineering approaches for understanding mechanical memory in cancer metastasis DOI Creative Commons
J. Lee, Andrew W. Holle

APL Bioengineering, Год журнала: 2024, Номер 8(2)

Опубликована: Апрель 10, 2024

Understanding cancer metastasis is crucial for advancing therapeutic strategies and improving clinical outcomes. Cancer cells face dynamic changes in their mechanical microenvironment that occur on timescales ranging from minutes to years exhibit a spectrum of cellular transformations response these cues. A facet this adaptive the concept memory, which mechanosensitive cell behavior function persists even when cues are altered. This review explores evolving landscape during metastasis, emphasizing significance memory its influence behavior. We then focus engineering techniques being utilized probe cells. Finally, we highlight promising translational approaches poised harness new therapies, thereby frontiers bioengineering applications research.

Язык: Английский

Процитировано

9
Spatially Resolved Niche and Tumor Microenvironmental Alterations in Gastric Cancer Peritoneal Metastases DOI Creative Commons
Joseph J. Zhao, Chin‐Ann Johnny Ong, Supriya Srivastava

и другие.

Gastroenterology, Год журнала: 2024, Номер 167(7), С. 1384 - 1398.e4

Опубликована: Авг. 13, 2024

Peritoneal metastasis (PM) in gastric cancer (GC) is associated with poor prognosis and significant morbidity. We sought to understand the genomic, transcriptomic, tumor microenvironment (TME) features that contribute peritoneal organotropism GC.

Язык: Английский

Процитировано

8
Biomechanics in the tumor microenvironment: from biological functions to potential clinical applications DOI Creative Commons
Hao Peng,

Zheng Chao,

Zefeng Wang

и другие.

Experimental Hematology and Oncology, Год журнала: 2025, Номер 14(1)

Опубликована: Янв. 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

Язык: Английский

Процитировано

1
Deciphering mechanical cues in the microenvironment: from non-malignant settings to tumor progression DOI Creative Commons
Yi‐Cheng Zhu,

Jiaoshun Chen,

Chen Chen

и другие.

Biomarker Research, Год журнала: 2025, Номер 13(1)

Опубликована: Янв. 23, 2025

The tumor microenvironment functions as a dynamic and intricate ecosystem, comprising diverse array of cellular non-cellular components that precisely orchestrate pivotal behaviors, including invasion, metastasis, drug resistance. While unraveling the interplay between behaviors represents tremendous challenge, recent research illuminates crucial biological phenomenon known mechanotransduction. Within microenvironment, mechanical cues like tensile stress, shear stiffness play role by activating mechanosensitive effectors such PIEZO proteins, integrins, Yes-associated protein. This activation initiates cascades intrinsic signaling pathways, effectively linking physical properties tissues to their physiological pathophysiological processes morphogenesis, regeneration, immunity. mechanistic insight offers novel perspective on how within impact behaviors. intricacies are yet be fully elucidated, it exhibits distinct attributes from non-malignant tissues, elevated solid stresses, interstitial hypertension, augmented matrix stiffness, enhanced viscoelasticity. These traits exert notable influences progression treatment responses, enriching our comprehension multifaceted nature microenvironment. Through this innovative review, we aim provide new lens decipher contexts, broadening knowledge these factors promote or inhibit thus offering valuable insights identify potential targets for anti-tumor strategies.

Язык: Английский

Процитировано

1
Matrix mechano-sensing at the invasive front induces a cytoskeletal and transcriptional memory supporting metastasis DOI Creative Commons
Óscar Maiques, Marta C. Sallán, Roman Laddach

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 14, 2025

The extracellular matrix (ECM) controls tumour dissemination. We characterise ECM organization in human and mouse tumours, identifying three regions: body, proximal invasive front distal front. Invasive areas show increased density, fibre thickness, length, alignment, with unique radial orientation at the correlating amoeboid features. Using patient samples murine models, we find that metastases recapitulate features of primary tumour. Ex vivo culture cancer cells isolated from different regions reveals a spatial cytoskeletal transcriptional memory. Several vitro models organisation showing induces 3D confinement supporting Rho-ROCK-Myosin II activity, while enhances directional invasion. Spatial transcriptomics identifies mechano-inflammatory program associated worse prognosis across multiple types. These findings provide mechanistic insights into how shapes local invasion distant metastasis. Interactions control tumor proliferation, Here, authors information on it influences cell metastasis properties through induction

Язык: Английский

Процитировано

1
Mechanical confinement governs phenotypic plasticity in melanoma DOI Open Access
Miranda V. Hunter, Emily Montal, Yilun Ma

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 2, 2024

ABSTRACT Phenotype switching is a form of cellular plasticity in which cancer cells reversibly move between two opposite extremes - proliferative versus invasive states. While it has long been hypothesised that such triggered by external cues, the identity these cues remained elusive. Here, we demonstrate mechanical confinement mediates phenotype through chromatin remodelling. Using zebrafish model melanoma coupled with human samples, profiled tumor at interface and surrounding microenvironment. Morphological analysis rare showed flattened, elliptical nuclei suggestive adjacent tissue. Spatial single-cell transcriptomics demonstrated adopted gene program neuronal invasion, including acquisition an acetylated tubulin cage protects nucleus during migration. We identified DNA-bending protein HMGB2 as confinement-induced mediator state. upregulated confined cells, quantitative modelling revealed prolongs contact time chromatin, leading to changes configuration favor phenotype. Genetic disruption regulates trade-off states, high are less but more drug resistant. Our results implicate microenvironment mechanism driving melanoma.

Язык: Английский

Процитировано

6
Personalized Vascularized Models of Breast Cancer Desmoplasia Reveal Biomechanical Determinants of Drug Delivery to the Tumor DOI Creative Commons
Giovanni S. Offeddu, Elena Cambria, Sarah E. Shelton

и другие.

Advanced Science, Год журнала: 2024, Номер 11(38)

Опубликована: Июль 23, 2024

Desmoplasia in breast cancer leads to heterogeneity physical properties of the tissue, resulting disparities drug delivery and treatment efficacy among patients, thus contributing high disease mortality. Personalized vitro models hold great promise for high-throughput testing therapeutic strategies normalize aberrant microenvironment a patient-specific manner. Here, tumoroids assembled from cell lines (MCF7, SKBR3, MDA-MB-468) patient-derived tumor cells (TCs) cultured microphysiological systems including perfusable microvasculature reproduce key aspects stromal vascular dysfunction causing impaired delivery. Models containing SKBR3 MDA-MB-468 show higher hyaluronic acid (HA) deposition, permeability, interstitial fluid pressure (IFP), degradation HA relative MCF7 or without tumoroids. Interleukin 8 (IL8) secretion is found responsible loss HA. Interventions targeting IL8 perfusion, IFP, ultimately enhance TC death response perfusion with trastuzumab cetuximab. Similar responses are observed models. These can be personalized by using applied discover new molecular therapies normalization microenvironment.

Язык: Английский

Процитировано

6