Cancer-Associated Fibroblasts Drive the Progression of Metastasis through both Paracrine and Mechanical Pressure on Cancer Tissue
Open accessAbstract
Neoplastic cells recruit fibroblasts through various growth factors and cytokines. These “cancer-associated fibroblasts” (CAF) actively interact with neoplastic cells and form a myofibroblastic microenvironment that promotes cancer growth and survival and supports malignancy. Several products of their paracrine signaling repertoire have been recognized as tumor growth and metastasis regulators. However, tumor-promoting cell signaling is not the only reason that makes CAFs key components of the “tumor microenvironment,” as CAFs affect both the architecture and growth mechanics of the developing tumor. CAFs participate in the remodeling of peritumoral stroma, which is a prerequisite of neoplastic cell invasion, expansion, and metastasis. CAFs are not present peritumorally as individual cells but they act orchestrated to fully deploy a desmoplastic program, characterized by “syncytial” (or collective) configuration and altered cell adhesion properties. Such myofibroblastic cohorts are reminiscent of those encountered in wound-healing processes. The view of “cancer as a wound that does not heal” led to useful comparisons between wound healing and tumorigenesis and expanded our knowledge of the role of CAF cohorts in cancer. In this integrative model of cancer invasion and metastasis, we propose that the CAF-supported microenvironment has a dual tumor-promoting role. Not only does it provide essential signals for cancer cell dedifferentiation, proliferation, and survival but it also facilitates cancer cell local invasion and metastatic phenomena. Mol Cancer Res; 10(11); 1403–18. ©2012 AACR.
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The localized exposure of stromal fibroblasts to TGF-β produced by cancer cells may involve filopodial extensions over several cell diameters.
“The localized exposure of stromal fibroblasts to TGF-β produced by cancer cells may involve filopodial extensions over several cell diameters243,244.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [243]
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Flagged first, then by citations
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Sorted by citations
Targeting the tumour stroma to improve cancer therapy
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- Authors
- Karagiannis, G. S., Poutahidis, T., Erdman, S. E., Kirsch, R., Riddell, R. H., & Diamandis, E. P.
- Affiliations
- Mount Sinai Hospital (CA)
- ORCID
- Venue
- Molecular Cancer Research
- Published
- 2012-11-15
- Volume
- 10
- Issue
- 11
- Pages
- 1403-1418
- ISSN
- 1541-7786 (ISSN-L)
- 1557-3125
- PMC
- PMC4399759
- OpenAlex
- W2123242217
- Cited by
- 507
- References
- 144
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 27 · 2023: 41 · 2022: 44 · 2021: 57 · 2020: 61 · 2019: 46 · 2018: 43 · 2017: 42 · 2016: 57 · 2015: 37 · 2014: 21 · 2013: 9 · 2012: 1
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Environmental Health Sciences (P30ES002109)
- Creations of Advanced Catalytic Transformation for the Sustainable Manufacturing at Low Energy, Low Environmental Load
- 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, metastasis, tumor microenvironment, paracrine signaling, mechanical pressure, desmoplasia, tumor invasion
- MeSH terms
- Fibroblasts, Humans, Neoplasm Metastasis, Neoplasms, Disease Progression, Paracrine Communication, Tumor Microenvironment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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