The role of tumor stroma in cancer progression and prognosis: Emphasis on carcinoma-associated fibroblasts and non-small cell lung cancer
Open accessAbstract
Maintenance of both normal epithelial tissues and their malignant counterparts is supported by the host tissue stroma. The tumor stroma mainly consists of the basement membrane, fibroblasts, extracellular matrix, immune cells, and vasculature. Although most host cells in the stroma possess certain tumor-suppressing abilities, the stroma will change during malignancy and eventually promote growth, invasion, and metastasis. Stromal changes at the invasion front include the appearance of carcinoma-associated fibroblasts (CAFs). CAFs constitute a major portion of the reactive tumor stroma and play a crucial role in tumor progression. The main precursors of CAFs are normal fibroblasts, and the transdifferentiation of fibroblasts to CAFs is driven to a great extent by cancer-derived cytokines such as transforming growth factor-β. During recent years, the crosstalk between the cancer cells and the tumor stroma, highly responsible for the progression of tumors and their metastasis, has been increasingly unveiled. A better understanding of the host stroma contribution to cancer progression will increase our knowledge about the growth promoting signaling pathways and hopefully lead to novel therapeutic interventions targeting the tumor stroma. This review reports novel data on the essential crosstalk between cancer cells and cells of the tumor stroma, with an emphasis on the role played by CAFs. Furthermore, it presents recent literature on relevant tumor stroma- and CAF-related resear…
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Tumor-associated stroma actively facilitates tumor initiation, invasion, and therapeutic resistance through biochemical and biomechanical means.
“While stroma in normal tissues may possess anti-tumor properties, tumor-associated stroma—comprising cancer-associated fibroblasts, ECM, endothelial cells, and immune cells—actively facilitates tumor initiation, invasion, and therapeutic resistance [139,140,141,142].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [142]
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- Authors
- Bremnes, R. M., Dønnem, T., Al-Saad, S., Al-Shibli, K., Andersen, S., Sirera, R., Camps, C., Marinez, I., & Busund, L.-T.
- Affiliations
- University Hospital of North Norway (NO)
- Nordland Hospital Trust (NO)
- Hospital General Universitario De Valencia (ES)
- UiT The Arctic University of Norway (NO)
- Corresponding author
- Bremnes, Roy M.
- Venue
- Journal of Thoracic Oncology
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 6
- Issue
- 1
- Pages
- 209-217
- ISSN
- 1556-0864 (ISSN-L)
- OpenAlex
- W2079347556
- Cited by
- 691
- References
- 10
- Citations by year
- 2026: 16 · 2025: 40 · 2024: 53 · 2023: 72 · 2022: 74 · 2021: 77 · 2020: 60 · 2019: 45 · 2018: 54 · 2017: 62 · 2016: 23 · 2015: 37 · 2014: 41 · 2013: 17 · 2012: 17
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Thoracic Oncology (publishedVersion)
- PubMed (publishedVersion)
- RiuNet (Universitat Politècnica de València) (submittedVersion, cc-by-nc-nd)
- 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
- tumor stroma, cancer-associated fibroblasts, non-small cell lung cancer, tumor progression, tumor microenvironment, fibroblast transdifferentiation, TGF-beta, extracellular matrix, metastasis, prognosis, stroma-targeted therapy
- MeSH terms
- Carcinoma, Non-Small-Cell Lung, Fibroblasts, Humans, Lung Neoplasms, Prognosis, Stromal Cells, Disease Progression
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