Extracellular matrix stiffness: mechanisms in tumor progression and therapeutic potential in cancer

Abstract Tumor microenvironment (TME) is a complex ecosystem composed of both cellular and non-cellular components that surround tumor tissue. The extracellular matrix (ECM) is a key component of the TME, performing multiple essential functions by providing mechanical support, shaping the TME, regul...

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Main Authors: Meiling Zhang, Bin Zhang
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Experimental Hematology & Oncology
Subjects:
Online Access:https://doi.org/10.1186/s40164-025-00647-2
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author Meiling Zhang
Bin Zhang
author_facet Meiling Zhang
Bin Zhang
author_sort Meiling Zhang
collection DOAJ
description Abstract Tumor microenvironment (TME) is a complex ecosystem composed of both cellular and non-cellular components that surround tumor tissue. The extracellular matrix (ECM) is a key component of the TME, performing multiple essential functions by providing mechanical support, shaping the TME, regulating metabolism and signaling, and modulating immune responses, all of which profoundly influence cell behavior. The quantity and cross-linking status of stromal components are primary determinants of tissue stiffness. During tumor development, ECM stiffness not only serves as a barrier to hinder drug delivery but also promotes cancer progression by inducing mechanical stimulation that activates cell membrane receptors and mechanical sensors. Thus, a comprehensive understanding of how ECM stiffness regulates tumor progression is crucial for identifying potential therapeutic targets for cancer. This review examines the effects of ECM stiffness on tumor progression, encompassing proliferation, migration, metastasis, drug resistance, angiogenesis, epithelial-mesenchymal transition (EMT), immune evasion, stemness, metabolic reprogramming, and genomic stability. Finally, we explore therapeutic strategies that target ECM stiffness and their implications for tumor progression.
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series Experimental Hematology & Oncology
spelling doaj-art-4777d6e288ac428b8a2d1094ba41774b2025-08-20T02:11:46ZengBMCExperimental Hematology & Oncology2162-36192025-04-0114113410.1186/s40164-025-00647-2Extracellular matrix stiffness: mechanisms in tumor progression and therapeutic potential in cancerMeiling Zhang0Bin Zhang1School of Basic Medicine, China Three Gorges UniversitySchool of Basic Medicine, China Three Gorges UniversityAbstract Tumor microenvironment (TME) is a complex ecosystem composed of both cellular and non-cellular components that surround tumor tissue. The extracellular matrix (ECM) is a key component of the TME, performing multiple essential functions by providing mechanical support, shaping the TME, regulating metabolism and signaling, and modulating immune responses, all of which profoundly influence cell behavior. The quantity and cross-linking status of stromal components are primary determinants of tissue stiffness. During tumor development, ECM stiffness not only serves as a barrier to hinder drug delivery but also promotes cancer progression by inducing mechanical stimulation that activates cell membrane receptors and mechanical sensors. Thus, a comprehensive understanding of how ECM stiffness regulates tumor progression is crucial for identifying potential therapeutic targets for cancer. This review examines the effects of ECM stiffness on tumor progression, encompassing proliferation, migration, metastasis, drug resistance, angiogenesis, epithelial-mesenchymal transition (EMT), immune evasion, stemness, metabolic reprogramming, and genomic stability. Finally, we explore therapeutic strategies that target ECM stiffness and their implications for tumor progression.https://doi.org/10.1186/s40164-025-00647-2Tumor microenvironmentExtracellular matrixStiffnessMechanical sensorCancer therapy
spellingShingle Meiling Zhang
Bin Zhang
Extracellular matrix stiffness: mechanisms in tumor progression and therapeutic potential in cancer
Experimental Hematology & Oncology
Tumor microenvironment
Extracellular matrix
Stiffness
Mechanical sensor
Cancer therapy
title Extracellular matrix stiffness: mechanisms in tumor progression and therapeutic potential in cancer
title_full Extracellular matrix stiffness: mechanisms in tumor progression and therapeutic potential in cancer
title_fullStr Extracellular matrix stiffness: mechanisms in tumor progression and therapeutic potential in cancer
title_full_unstemmed Extracellular matrix stiffness: mechanisms in tumor progression and therapeutic potential in cancer
title_short Extracellular matrix stiffness: mechanisms in tumor progression and therapeutic potential in cancer
title_sort extracellular matrix stiffness mechanisms in tumor progression and therapeutic potential in cancer
topic Tumor microenvironment
Extracellular matrix
Stiffness
Mechanical sensor
Cancer therapy
url https://doi.org/10.1186/s40164-025-00647-2
work_keys_str_mv AT meilingzhang extracellularmatrixstiffnessmechanismsintumorprogressionandtherapeuticpotentialincancer
AT binzhang extracellularmatrixstiffnessmechanismsintumorprogressionandtherapeuticpotentialincancer