A framework for advancing our understanding of cancer-associated fibroblasts

Nature reviews. Cancer, Journal Year: 2020, Volume and Issue: 20(3), P. 174 - 186

Published: Jan. 24, 2020

Abstract Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment with diverse functions, including matrix deposition and remodelling, extensive reciprocal signalling interactions cancer cells crosstalk infiltrating leukocytes. As such, they potential target for optimizing therapeutic strategies against cancer. However, many challenges present in ongoing attempts to modulate CAFs benefit. These include limitations our understanding origin heterogeneity CAF function, it being desirable retain some antitumorigenic functions. On basis meeting experts field biology, we summarize this Consensus Statement current knowledge framework advancing critical cell type within microenvironment.

Language: Английский

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Effects of extracellular matrix viscoelasticity on cellular behaviour

Nature, Journal Year: 2020, Volume and Issue: 584(7822), P. 535 - 546

Published: Aug. 26, 2020

Language: Английский

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Extracellular Matrix in the Tumor Microenvironment and Its Impact on Cancer Therapy

Frontiers in Molecular Biosciences, Journal Year: 2020, Volume and Issue: 6

Published: Jan. 30, 2020

Solid tumors are complex organ-like structures that consist not only of tumor cells but also vasculature, extracellular matrix (ECM), stromal and immune cells. Often this microenvironment (TME), comprises the larger part overall mass. Like other components TME ECM in solid differs significantly from normal organs. Intratumoral signaling, transport mechanisms, metabolisms, oxygenation, immunogenicity strongly affected if controlled by ECM. Exerting regulatory control, does influence malignancy growth its response towards therapy. Understanding particularities is necessary to develop approaches interfere with negative effect. In review, we will highlight current understanding physical, cellular molecular mechanisms which pathological affects efficiency radio-, chemo- immunotherapy. Finally, discuss various strategies target modify how they could be utilized improve

Language: Английский

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Mechanisms of 3D cell migration

Nature Reviews Molecular Cell Biology, Journal Year: 2019, Volume and Issue: 20(12), P. 738 - 752

Published: Oct. 3, 2019

Language: Английский

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The matrix in cancer

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(4), P. 217 - 238

Published: Feb. 15, 2021

Language: Английский

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A guide to the composition and functions of the extracellular matrix

FEBS Journal, Journal Year: 2021, Volume and Issue: 288(24), P. 6850 - 6912

Published: Feb. 21, 2021

Extracellular matrix (ECM) is a dynamic 3‐dimensional network of macromolecules that provides structural support for the cells and tissues. Accumulated knowledge clearly demonstrated over last decade ECM plays key regulatory roles since it orchestrates cell signaling, functions, properties morphology. Extracellularly secreted as well cell‐bound factors are among major members family. Proteins/glycoproteins, such collagens, elastin, laminins tenascins, proteoglycans glycosaminoglycans, hyaluronan, their receptors CD44 integrins, responsible adhesion, comprise well‐organized functional with significant in health disease. On other hand, enzymes metalloproteinases specific glycosidases including heparanase hyaluronidases contribute to remodeling affect human health. Several processes them proliferation survival, migration, differentiation, autophagy, angiogenesis, immunity regulation affected by certain components. Structural alterations have been also associated disease progression. This guide on composition functions gives broad overview matrisome, macromolecules, interaction networks within surface, summarizes main features tissue organization emphasizes importance constituents development progression advances molecular targeting design new therapeutic strategies.

Language: Английский

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Physical traits of cancer

Science, Journal Year: 2020, Volume and Issue: 370(6516)

Published: Oct. 29, 2020

The role of the physical microenvironment in tumor development, progression, metastasis, and treatment is gaining appreciation. emerging multidisciplinary field sciences cancer now embraced by engineers, physicists, cell biologists, developmental oncologists attempting to understand how parameters processes affect progression treatment. Discoveries this are starting be translated into new therapeutic strategies for cancer. In Review, we propose four traits tumors that contribute resistance: (i) elevated solid stresses (compression tension), (ii) interstitial fluid pressure, (iii) altered material properties (for example, increased tissue stiffness, which historically has been used detect palpation), (iv) microarchitecture. After defining these traits, discuss their causes, consequences, they complement biological hallmarks

Language: Английский

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Targeting integrin pathways: mechanisms and advances in therapy

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Jan. 2, 2023

Abstract Integrins are considered the main cell-adhesion transmembrane receptors that play multifaceted roles as extracellular matrix (ECM)-cytoskeletal linkers and transducers in biochemical mechanical signals between cells their environment a wide range of states health diseases. Integrin functions dependable on delicate balance active inactive status via multiple mechanisms, including protein-protein interactions, conformational changes, trafficking. Due to exposure cell surface sensitivity molecular blockade, integrins have been investigated pharmacological targets for nearly 40 years, but given complexity sometimes opposite characteristics, targeting integrin therapeutics has challenge. To date, only seven drugs successfully marketed, abciximab, eptifibatide, tirofiban, natalizumab, vedolizumab, lifitegrast, carotegrast. Currently, there approximately 90 kinds integrin-based therapeutic or imaging agents clinical studies, small molecules, antibodies, synthetic mimic peptides, antibody–drug conjugates (ADCs), chimeric antigen receptor (CAR) T-cell therapy, agents, etc. A serious lesson from past drug discovery research efforts is successes rely both deep understanding integrin-regulatory mechanisms unmet needs. Herein, we provide systematic complete review all family members integrin-mediated downstream signal transduction highlight ongoing develop new therapies/diagnoses bench clinic. In addition, further discuss trend development, how improve success rate trials therapies, key points research, basic translational research.

Language: Английский

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The nucleus acts as a ruler tailoring cell responses to spatial constraints

Science, Journal Year: 2020, Volume and Issue: 370(6514)

Published: Oct. 16, 2020

The nucleus makes the rules Single cells continuously experience and react to mechanical challenges in three-dimensional tissues. Spatial constraints dense tissues, physical activity, injury all impose changes cell shape. How can measure shape deformations ensure correct tissue development homeostasis remains largely unknown (see Perspective by Shen Niethammer). Working independently, Venturini et al. Lomakin now show that act as an intracellular ruler cellular variations. nuclear envelope provides a gauge of deformation activates mechanotransduction pathway controls actomyosin contractility migration plasticity. thereby allows adapt their behavior local microenvironment. Science , this issue p. eaba2644 eaba2894 ; see also 295

Language: Английский

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Cytoskeletal Crosstalk in Cell Migration

Trends in Cell Biology, Journal Year: 2020, Volume and Issue: 30(9), P. 720 - 735

Published: July 13, 2020

Language: Английский

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