INTERNATIONAL CONGRESS OF
CancerGenetics
Role of Cancer-Associated Fibroblasts in Cancer Progression
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Mehrdad Ostadpoor,1,* Majid Gholami-Ahangaran,2
1. Graduated of Veterinary Medicine Faculty, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
2. Associate Professor, Group of Clinical Sciences, Faculty of Veterinary Medicine, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
- Introduction: Fibroblasts play key roles in disease, tissue homeostasis, cancer progression, inflammatory and fibrotic conditions, and wound healing processes. Cancer-associated fibroblasts (CAFs) are a major component of the stroma and secrete growth factors, inflammatory ligands, and extracellular matrix (ECM) proteins that promote tumor proliferation, therapy resistance, and immune exclusion. CAFs regulate the biology of tumor cells and other stromal cells via cell–cell contact, releasing numerous regulatory factors and synthesizing and re-modelling the extracellular matrix, and thus these cells affect cancer initiation and development. Promoting the proliferation, invasion and migration of cancer cells is a major way of CAFs to facilitate cancer development. Cytokines secreted by CAFs that have been implicated in this process include TGF-β, interleukin-1α (IL-1α), IL-6, interleukin-33 (IL-33), stromal cell-derived factor 1 (SDF1), C-X-C motif chemokine ligand 8 (CXCL8), and cyclooxygenase-2 (COX-2), and different molecules mediate diverse effects.
- Methods: In the current study, keywords including Cancer-Associated Fibroblasts, Cancer, and Progression were reviewed from the list of Mesh and other credible websites including PubMed, Science Direct, and Google Scholar, and the data was organized. The searches comprised all published papers from 2010 to 2023. All of the full text was considered, and the papers manifested as only abstract were excluded. The full papers selected focused on the specific role of cancer-associated fibroblasts in cancer progression only. A total of 50 papers were selected and studied in this review.
- Results: Articles showed that cross-talk between tumorigenic cells and fibroblasts may be responsible for the emergence of a subpopulation of hyper-activated fibroblasts that are present in the tumor microenvironment (TME). Some studies have shown that CAFs are highly heterogeneous and have been shown to enhance cellular migration and alter metabolism of epithelial tumor cells, display elevated pro-angiogenic cytokine signaling, regulate the plasticity of cancer stem cells, play a significant role in the development of drug resistance, and facilitate inflammation. Recent studies revealed that instead of cancer cells, CAFs contribute to tumor proliferation, invasion, and metastasis via secretion of various growth factors, cytokines, chemokines, and degradation of extracellular matrix (ECM) proteins. Previous studies using genetically engineered mouse models (GEMMs) of pancreatic cancer have shown that CAFs and ECM produced by CAFs confer resistance to chemotherapy by impairing efficient drug delivery. Certain studies have suggested that the mesenchymal-like phenotype of CAFs is involved in enhancing the metastasis of cancer cells. Articles showed secretion of TGF-β by CAFs promotes the EMT of breast cancer cells via TGF-β/SMAD and non-SMAD signaling pathways and facilitates tumor growth and metastasis in colorectal cancer. Studies on cancer immunotherapy have shed light on the involvement of CAF in the tumor immune microenvironment and have revealed that CAF expressing fibroblast activation protein-α (FAPα) or α-smooth muscle actin (α-SMA) suppress antitumor immunity through various mechanisms, contributing to the formation of a tumor-permissive microenvironment.
- Conclusion: Cancer-associated fibroblasts (CAFs) are a major component of tumor stroma and play a crucial role in the proliferation, invasiveness, metastasis, and angiogenesis of cancer. CAFs promote cancer progression through multiple mechanisms, including extracellular matrix (ECM) remodeling and the production of growth factors, cytokines, and chemokines, which promote cancer cell proliferation, metabolism, and tumor angiogenesis.
- Keywords: Cancer-Associated Fibroblasts, Cancer, Progression
