Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 13, 2025

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.

Language: Английский

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Multiple aspects of matrix stiffness in cancer progression

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: July 2, 2024

The biophysical and biomechanical properties of the extracellular matrix (ECM) are crucial in processes cell differentiation proliferation. However, it is unclear to what extent tumor cells influenced by changes surrounding microenvironment how this response varies between different forms, over course progression. entire ensemble genes encoding ECM associated proteins called matrisome. In cancer, evolves become highly dysregulated, rigid, fibrotic, serving both pro-tumorigenic anti-tumorigenic roles. Tumor desmoplasia characterized a dramatic increase α-smooth muscle actin expressing fibroblast deposition hard containing collagen, fibronectin, proteoglycans, hyaluronic acid common many solid tumors. review, we described role inflammation inflammatory cytokines, desmoplastic remodeling, state transition driven forces signaling pathways mechanotransduction as potential targeted therapies, focusing on impact qualitative quantitative variations regulation development, hypothesizing presence matrisome drivers, acting alongside cell-intrinsic oncogenic some stages neoplastic progression contexts, such pancreatic carcinoma, breast lung cancer mesothelioma.

Language: Английский

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The mechanopathology of the tumor microenvironment: detection techniques, molecular mechanisms and therapeutic opportunities

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: March 18, 2025

The mechanical properties of the tumor microenvironment (TME) undergo significant changes during growth, primarily driven by alterations in extracellular (ECM) stiffness and viscoelasticity. These not only promote progression but also hinder therapeutic efficacy impairing drug delivery activating mechanotransduction pathways that regulate crucial cellular processes such as migration, proliferation, resistance to therapy. In this review, we examine mechanisms through which cells sense transmit signals maintain homeostasis biomechanically altered TME. We explore current computational modelling strategies for pathways, highlighting need developing models incorporate additional components mechanosignaling machinery. Furthermore, review available methods measuring tumors clinical settings aiming at restoring TME blocking deregulated pathways. Finally, propose proper characterization a deeper understanding landscape TME, both tissue levels, are essential account influence forces on treatment efficacy.

Language: Английский

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Effects of mechanical ventilation on the interstitial extracellular matrix in healthy lungs and lungs affected by acute respiratory distress syndrome: a narrative review

Critical Care, Journal Year: 2024, Volume and Issue: 28(1)

Published: May 15, 2024

Abstract Background Mechanical ventilation, a lifesaving intervention in critical care, can lead to damage the extracellular matrix (ECM), triggering inflammation and ventilator-induced lung injury (VILI), particularly conditions such as acute respiratory distress syndrome (ARDS). This review discusses detailed structure of ECM healthy ARDS-affected lungs under mechanical aiming bridge gap between experimental insights clinical practice by offering thorough understanding organization dynamics its alteration during ventilation. Main text Focusing on implications, we explore potential precise interventions targeting cellular signaling pathways mitigate damage, reduce inflammation, ultimately improve outcomes for critically ill patients. By analyzing range studies papers, particular attention is paid roles metalloproteinases (MMPs), integrins, other molecules VILI. synthesis not only sheds light structural changes induced stress but also underscores importance responses fibrosis, excessive activation MMPs. Conclusions emphasizes significance cues transduced integrins their impact behavior into complex interactions signaling. these mechanisms, healthcare professionals care anticipate consequences ventilation use targeted strategies prevent or minimize leading better patient management settings.

Language: Английский

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Bioprinting of Cells, Organoids and Organs-on-a-Chip Together with Hydrogels Improves Structural and Mechanical Cues

Cells, Journal Year: 2024, Volume and Issue: 13(19), P. 1638 - 1638

Published: Oct. 1, 2024

The 3D bioprinting technique has made enormous progress in tissue engineering, regenerative medicine and research into diseases such as cancer. Apart from individual cells, a collection of organoids, can be printed combination with various hydrogels. It hypothesized that will even become promising tool for mechanobiological analyses organoids their matrix environments highly defined precisely structured environments, which the mechanical properties cell environment individually adjusted. Mechanical obstacles or bead markers integrated bioprinted samples to analyze deformations forces within these constructs, perform biophysical analysis complex systems, are still not standard techniques. review highlights advances 4D printing technologies integrating cues so next step detailed key future directions organoid generation development disease model regeneration drug testing perspective. Finally, hydrogels, pure natural synthetic hydrogels mixtures, organoid–cell co-cultures, organ-on-a-chip systems organoid-organ-on-a chip combinations introduces use assembloids determine mutual interactions different types cell–matrix interferences specific biological environments.

Language: Английский

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Vascular Extracellular Matrix in Atherosclerosis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12017 - 12017

Published: Nov. 8, 2024

The extracellular matrix (ECM) plays a central role in the structural integrity and functionality of cardiovascular system. Moreover, ECM is involved atherosclerotic plaque formation stability. In fact, remodeling affects stability, cellular migration, inflammatory responses. Collagens, fibronectin, laminin, elastin, proteoglycans are crucial proteins during atherosclerosis development. This dynamic driven by proteolytic enzymes such as metalloproteinases (MMPs), cathepsins, serine proteases. Exploring investigating dynamics an important step to designing innovative therapeutic strategies targeting mechanisms, thus offering significant advantages management diseases. review illustrates structure vascular ECM, presenting new perspective on its potential target treatments.

Language: Английский

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Penile Cancer: Innovations in Ultrastructural and Vibrational Markers

ACS Omega, Journal Year: 2025, Volume and Issue: 10(4), P. 3449 - 3461

Published: Jan. 23, 2025

Penile cancer (PCa) is a disease that manifests predominantly as squamous cell carcinomas (SCCs), which, although rare, represents significant public health problem, especially in regions with less socioeconomic development. One of the biggest challenges managing this difficulty differentiating tumor subtypes, making accurate diagnosis and treatment challenging. In context, new characterization techniques are needed to investigate these tumors more completely. Atomic force microscopy (AFM) Raman spectroscopy (RS) valuable providing quantitative qualitative ultrastructural data vibrational signatures analyzed samples. study, AFM RS were employed subtypes penile cancer, including highly aggressive basaloid subtype, which closely associated human papillomavirus (HPV), sarcomatoid comparing them nontumorous tissues. The results revealed nanoscale changes properties samples, such increased roughness tissues, emphasis on type HPV virus, reduction surface area volume tissues at nanoscale, suggesting deeper tissue infiltration greater deformability samples nanoscale. detected spectral differences between normal cancerous particularly modes related proteins lipids. Principal component analysis (PCA) confirmed strong discriminative power control PCa groups. presented here offers insights into characteristics that, when integrated clinical analyses, could improve understanding behavior, contributing diagnostic methods targeted treatments.

Language: Английский

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Integrin and Its Associated Proteins as a Mediator for Mechano-Signal Transduction

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 166 - 166

Published: Jan. 23, 2025

Mechano-signal transduction is a process in which cells perceive extracellular mechanical signals, convert them into intracellular biochemical and produce response. Integrins are cell surface receptors that sense the cues bind to matrix (ECM). This binding induces integrin clustering activation. Cytoplasmic tails of activated integrins interact induce cytoskeleton tensions via several adaptor proteins. monitor stiffness modulate ECM downstream signaling pathways regulating expression genes components. Integrin-mediated mechano-transduction very crucial for as it regulates physiology both normal diseased conditions according cues. It proliferation, survival, migration. Abnormal such extreme prolonged stress result pathological including fibrosis, cancers, skin, autoimmune disorders. paper aims explore role their associated proteins mechano-signal transduction. highlights targets therapy development. Furthermore, also presents challenges targeted drug development, can be resistance cytotoxicity. concluded this research on integrin-mediated its relationship with pathologies will an important step towards development effective therapies.

Language: Английский

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RhoA and Rac1 as Mechanotransduction Mediators in Colorectal Cancer

Advanced Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Abstract Colorectal cancer (CRC) remains a leading cause of cancer‐related deaths, creating an urgent need for innovative diagnostic solutions. Mechanobiology, cutting‐edge field that investigates how physical forces influence cell behavior, is now revealing new insights into progression. This research focuses on two crucial players: RhoA and Rac1, small yet powerful proteins regulate the structure movement cells. controls adhesion migration, while Rac1 drives invasion. As CRC tumors grow reshape colon's mechanical environment, these pathways become disrupted, accelerating Examining level in clinical samples under strain reveals their potential as markers. Tracking activity can unlock valuable dissemination, offering avenues understanding diagnosing CRC. approach holds promise earlier detection better outcomes by key more effective strategies.

Language: Английский

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Existence of weak solutions for a volume-filling model of cell invasion into extracellular matrix

Journal of Differential Equations, Journal Year: 2025, Volume and Issue: 428, P. 721 - 746

Published: Feb. 14, 2025

Language: Английский

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