The role of cancer-associated fibroblasts, solid stress and other microenvironmental factors in tumor progression and therapy resistance
Open accessAbstract
Tumors are not merely masses of neoplastic cells but complex tissues composed of cellular and noncellular elements. This review provides recent data on the main components of a dynamic system, such as carcinoma associated fibroblasts that change the extracellular matrix (ECM) topology, induce stemness and promote metastasis-initiating cells. Altered production and characteristics of collagen, hyaluronan and other ECM proteins induce increased matrix stiffness. Stiffness along with tumor growth-induced solid stress and increased interstitial fluid pressure contribute to tumor progression and therapy resistance. Second, the role of immune cells, cytokines and chemokines is outlined. We discuss other noncellular characteristics of the tumor microenvironment such as hypoxia and extracellular pH in relation to neoangiogenesis. Overall, full understanding of the events driving the interactions between tumor cells and their environment is of crucial importance in overcoming treatment resistance and improving patient outcome.
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Fibroblasts respond to chemotactic signals such as TGF-β, PDGF, and CXCL12, which are differentially distributed within tumors and drive directed migration toward tumor cores.
“fibroblasts respond to a variety of chemotactic signals such as TGF-β, PDGF, and CXCL12, which are differentially distributed within tumors and further drive their directed migration toward tumor cores [286].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [286]
The Background section on fibroblasts says TGF-β affects fibroblasts, and the section on matrix topology describes directional cell migration guided by physical cues. But the paper does not say that TGF-β, PDGF, and CXCL12 form differential distributions that direct fibroblasts toward tumor cores; its discussion of CXCL12 concerns attraction of immune cells, not fibroblasts. (LLM, conf=0.82)
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- Authors
- Kharaishvili, G., Simkova, D., Bouchalova, K., Gachechiladze, M., Narsia, N., & Bouchal, J.
- Affiliations
- Institute of Molecular and Translational Medicine (CZ)
- University of Birmingham (GB)
- Corresponding author
- Bouchal, Jan
- Venue
- Cancer Cell International
- Published
- 2014-05-16
- Volume
- 14
- Issue
- 1
- Pages
- 41-41
- ISSN
- 1475-2867 (ISSN-L)
- PMC
- PMC4038849
- OpenAlex
- W2150704193
- Cited by
- 197
- References
- 110
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 11 · 2023: 12 · 2022: 14 · 2021: 11 · 2020: 8 · 2019: 22 · 2018: 27 · 2017: 19 · 2016: 20 · 2015: 34 · 2014: 3
- FWCI
- 2.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Cancer Cell International (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- cancer-associated fibroblasts, tumor microenvironment, extracellular matrix stiffness, solid stress, interstitial fluid pressure, treatment resistance, tumor progression, metastasis-initiating cells, stemness, collagen, hyaluronic acid, tumor hypoxia, extracellular pH, neoangiogenesis, immune cells, cytokines, chemokines
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