Cancer-associated fibroblasts in tumor microenvironment–Accomplices in tumor malignancy
Abstract
There is much cellular heterogeneity in the tumor microenvironment. The tumor epithelia and stromal cells co-evolve, and this reciprocal relationship dictates almost every step of cancer development and progression. Despite this, many anticancer therapies are designed around druggable features of tumor epithelia, ignoring the supportive role of stromal cells. Cancer-associated fibroblasts (CAFs) are the dominant cell type within the reactive stroma of many tumor types. Numerous previous studies have highlighted a pro-tumorigenic role for CAFs via secretion of various growth factors, cytokines, chemokines, and the degradation of extracellular matrix. Recent works showed that CAFs secrete H 2 O 2 to effect stromal-mediated field cancerization, transform primary epithelial cells, and aggravate cancer cell aggressiveness, in addition to inflammatory and mitogenic factors. Molecular characterization of CAFs also underscores the importance of Notch and specific nuclear receptor signaling in the activation of CAFs. This review consolidates recent findings of CAFs and highlights areas for future investigations.
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Metabolic disorders including cardiometabolic syndrome (CMS), diabetes, cardiovascular disease (CVD), and cancer are common comorbidities of sarcopenic obesity.
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- Authors
- Liao, Z., Tan, Z. W., Zhu, P., & Tan, N. S.
- Affiliations
- Nanyang Technological University (SG)
- Agency for Science, Technology and Research (SG)
- Corresponding author
- Tan, Zhen Wei
- Tan, Nguan Soon
- Venue
- Cellular Immunology
- Publisher
- Elsevier BV
- Published
- 2019-09
- Volume
- 343
- Pages
- 103729
- ISSN
- 0008-8749 (ISSN-L)
- OpenAlex
- W2789705845
- Cited by
- 335
- References
- 198
- Citations by year
- 2026: 18 · 2025: 33 · 2024: 49 · 2023: 61 · 2022: 55 · 2021: 52 · 2020: 28 · 2019: 24 · 2018: 13
- FWCI
- 3.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cellular Immunology (publishedVersion)
- PubMed (publishedVersion)
- DR-NTU (Nanyang Technological University) (submittedVersion)
- Funders
- Ministry of Education - Singapore (MOE2012-T1-001-036, MOE2014-T2-1-012, RG134/15)
- 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, reactive stroma, tumor progression, extracellular matrix degradation, hydrogen peroxide, field cancerization, epithelial transformation, Notch signaling, nuclear receptor signaling, tumor inflammation, stromal-epithelial crosstalk
- MeSH terms
- Cancer-Associated Fibroblasts, Animals, Humans, Neoplasms, Tumor Microenvironment, Carcinogenesis
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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