Activation of fibroblasts in cancer stroma
Abstract
Tumor microenvironment has emerged as an important target for cancer therapy. In particular, cancer-associated fibroblasts (CAF) seem to regulate many aspects of tumorigenesis. CAFs secrete a variety of soluble factors that act in a paracrine manner and thus affect not only cancer cells, but also other cell types present in the tumor stroma. Acting on cancer cells, CAFs promote tumor growth and invasion. They also enhance angiogenesis by secreting factors that activate endothelial cells and pericytes. Tumor immunity is mediated via cytokines secreted by immune cells and CAFs. Both immune cells and CAFs can exert tumor-suppressing and -promoting effects. CAFs, and the factors they produce, are attractive targets for cancer therapy, and they have proven to be useful as prognostic markers. In this review we focus mainly on carcinomas and discuss the recent findings regarding the role of activated fibroblasts in driving tumor progression.
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Tumor cells actively reprogram surrounding fibroblasts into cancer-associated fibroblasts (CAFs).
“With the advancement of tumor biology, it became clear that tumor cells actively reprogram surrounding fibroblasts into a modified state termed cancer-associated fibroblasts (CAFs) [5,19,35,36].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [35]
CAFs may also originate from bone marrow-derived mesenchymal stem cells, epithelial-mesenchymal transition of epithelial cells, and endothelial cells that undergo endothelial-to-mesenchymal transition.
“CAFs may also originate from bone marrow‐derived mesenchymal stem cells,[ 20 ] epithelial‐mesenchymal transition (EMT) of epithelial cells,[ 21 ] and endothelial cells that undergo endothelial‐to‐mesenchymal transition.[ 22 ]”
From 3D Biomimetic Models to Reconstitute Tumor Microenvironment In Vitro: Spheroids, Organoids, and Tumor‐on‐a‐Chip (2023) · cites this paper as [22]
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- Authors
- Räsänen, K., & Vaheri, A.
- Affiliations
- University of Helsinki (FI)
- Corresponding author
- Räsänen, Kati
- ORCID
- Vaheri, Antti
- Venue
- Experimental Cell Research
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 316
- Issue
- 17
- Pages
- 2713-2722
- ISSN
- 0014-4827 (ISSN-L)
- OpenAlex
- W2082503761
- Cited by
- 499
- References
- 16
- Citations by year
- 2026: 11 · 2025: 9 · 2024: 20 · 2023: 19 · 2022: 30 · 2021: 44 · 2020: 39 · 2019: 37 · 2018: 29 · 2017: 25 · 2016: 36 · 2015: 44 · 2014: 40 · 2013: 45 · 2012: 42
- FWCI
- 4.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Experimental Cell Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Magnus Ehrnroothin Säätiö
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- cancer-associated fibroblasts, tumor microenvironment, tumor stroma, paracrine signaling, tumor angiogenesis, tumor invasion, antitumor immunity, carcinoma, tumor progression, cancer therapy targets, prognostic factors
- MeSH terms
- Fibroblasts, Humans, Neoplasms, Stromal Cells, Paracrine Communication
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