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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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“Secondly, metabolic disorders including cardiometabolic syndrome (CMS), diabetes, cardiovascular disease (CVD), and cancer are common comorbidities of SO (54, 55).”
From Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments (2020) · cites this paper as [55]
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Николаевна, Д. И., Lukina, M. M., Dudenkova, V. V., Ignatova, N. I., Shirmanova, M. V., & Вадимовна, З. Е. (2019) · Nauchno-prakticheskii zhurnal «Patogenez» · doi:10.25557/2310-0435.2019.04.33-42
Understanding wound healing and cancer in the skin
Tan, M. W. Y. (2020) · DR-NTU (Nanyang Technological University) · doi:10.32657/10356/142075
Metadata
- 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
- 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
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