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Extracellular Matrix Remodeling and Stiffening Modulate Tumor Phenotype and Treatment Response
Abstract
Solid tumors are characterized by a remodeled and stiffened extracellular matrix. The extracellular matrix is not a passive by-product of the tumor, but actively compromises tissue-specific differentiation, enhances tumor cell proliferation and survival, and fosters tumor cell invasion and migration. The tumor extracellular matrix also influences the behavior of the stromal cells, which through vicious, feedforward-reinforcing pathways promote tumor progression and compromise treatment efficacy. To investigate how the tumor extracellular matrix alters cancer phenotype and treatment, a number of three-dimensional, organotypic culture models have been developed that employ a variety of materials, including natural matrices, collagen, fibrin, and reconstituted basement membrane gels, as well as synthetic hydrogel materials such as polyacrylamide and polyethylene glycol. These models have been used to interrogate how specific microenvironmental features modify tumor and stromal cell function and to identify the molecular mechanisms that regulate tumorigenesis and therapeutic efficacy. To translate these findings into more effective treatment strategies for patients, clinically informed studies are needed that incorporate computational modeling and in vivo validation.
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“which was comparable to the tissues of collagen fibers, osteoid and pre-calcified bone respectively [8,33,34].”
From Substrate stiffness modulates bone marrow-derived macrophage polarization through NF-κB signaling pathway (2020) · cites this paper as [34]
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Metadata
- Authors
- Leight, J. L., Drain, A. P., & Weaver, V. M.
- Affiliations
- The Ohio State University (US)
- University of California, San Francisco (US)
- Venue
- Annual Review of Cancer Biology
- Publisher
- Annual Reviews
- Published
- 2017-03-06
- Volume
- 1
- Issue
- 1
- Pages
- 313-334
- ISSN
- 2472-3428 (ISSN-L)
- OpenAlex
- W2511694260
- Cited by
- 131
- References
- 20
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 15 · 2023: 17 · 2022: 21 · 2021: 13 · 2020: 22 · 2019: 17 · 2018: 10 · 2017: 6
- FWCI
- 1.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Cancer Biology (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- extracellular matrix remodeling, tumor stiffness, tumor microenvironment, tumor stroma, organotypic culture model, 3D tumor models, collagen, fibrin, hydrogels, tumor cell migration and invasion, treatment response, tumor progression, computational modeling
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- The paper
- Leight, J. L., Drain, A. P., & Weaver, V. M. (2017). Extracellular Matrix Remodeling and Stiffening Modulate Tumor Phenotype and Treatment Response. Annual Review of Cancer Biology. https://doi.org/10.1146/annurev-cancerbio-050216-034431
