Stroma-Derived Three-Dimensional Matrices Are Necessary and Sufficient to Promote Desmoplastic Differentiation of Normal Fibroblasts
Open accessAbstract
Stromagenesis is a host reaction of connective tissue that, when induced in cancer, produces a progressive and permissive mesenchymal microenvironment, thereby supporting tumor progression. The stromal microenvironment is complex and comprises several cell types, including fibroblasts, the primary producers of the noncellular scaffolds known as extracellular matrices. The events that support tumor progression during stromagenesis are for the most part unknown due to the lack of suitable, physiologically relevant, experimental model systems. In this report, we introduce a novel in vivo-like three-dimensional system derived from tumor-associated fibroblasts at diverse stages of tumor development that mimic the stromagenic features of fibroblasts and their matrices observed in vivo. Harvested primary stromal fibroblasts, obtained from different stages of tumor development, did not retain in vivo stromagenic characteristics when cultured on traditional two-dimensional substrates. However, they were capable of effectively maintaining the tumor-associated stromal characteristics within three-dimensional cultures. In this study, we demonstrate that in vivo-like three-dimensional matrices appear to have the necessary topographical and molecular information sufficient to induce desmoplastic stroma differentiation of normal fibroblasts.
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Physical changes in the ECM are capable of activating CAFs.
“Physical changes in the ECM are also capable of activating CAFs53,61–64.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [62]
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- Authors
- Amatangelo, M. D., Bassi, D. E., Klein-Szanto, A. J. P., & Cukierman, E.
- Affiliations
- Fox Chase Cancer Center (US)
- Corresponding author
- Cukierman, Edna
- ORCID
- Cukierman, Edna
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2005-08
- Volume
- 167
- Issue
- 2
- Pages
- 475-488
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC1603576
- OpenAlex
- W2112910223
- Cited by
- 248
- References
- 62
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 14 · 2023: 11 · 2022: 12 · 2021: 8 · 2020: 17 · 2019: 13 · 2018: 10 · 2017: 22 · 2016: 13 · 2015: 11 · 2014: 15 · 2013: 18 · 2012: 17
- FWCI
- 2.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA006927, 1 R21 CA109442-01)
- American Association for Cancer Research
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- desmoplasia, cancer-associated fibroblasts, extracellular matrix, 3D cell culture, normal fibroblasts, tumor microenvironment, topography, tumor stroma
- MeSH terms
- Animals, Carcinoma, Squamous Cell, Cell Communication, Cell Differentiation, Extracellular Matrix, Fibroblasts, Models, Biological, Skin Neoplasms, 9,10-Dimethyl-1,2-benzanthracene, Stromal Cells, Disease Progression, Mice
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