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Fibroblasts in the Tumor Microenvironment: Shield or Spear?
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2018 May 21; Vol. 19 (5). Date of Electronic Publication: 2018 May 21. - Publication Year :
- 2018
-
Abstract
- Tumorigenesis is a complex process involving dynamic interactions between malignant cells and their surrounding stroma, including both the cellular and acellular components. Within the stroma, fibroblasts represent not only a predominant cell type, but also a major source of the acellular tissue microenvironment comprising the extracellular matrix (ECM) and soluble factors. Normal fibroblasts can exert diverse suppressive functions against cancer initiating and metastatic cells via direct cell-cell contact, paracrine signaling by soluble factors, and ECM integrity. The loss of such suppressive functions is an inherent step in tumor progression. A tumor cell-induced switch of normal fibroblasts into cancer-associated fibroblasts (CAFs), in turn, triggers a range of pro-tumorigenic signals accompanied by distraction of the normal tissue architecture, thus creating an optimal niche for cancer cells to grow extensively. To further support tumor progression and metastasis, CAFs secrete factors such as ECM remodeling enzymes that further modify the tumor microenvironment in combination with the altered adhesive forces and cell-cell interactions. These paradoxical tumor suppressive and promoting actions of fibroblasts are the focus of this review, highlighting the heterogenic molecular properties of both normal and cancer-associated fibroblasts, as well as their main mechanisms of action, including the emerging impact on immunomodulation and different therapy responses.
- Subjects :
- Animals
Cancer-Associated Fibroblasts cytology
Cancer-Associated Fibroblasts immunology
Cancer-Associated Fibroblasts metabolism
Disease Progression
Extracellular Matrix immunology
Extracellular Matrix metabolism
Extracellular Matrix pathology
Humans
Immunomodulation
Neoplasm Invasiveness immunology
Neoplasm Invasiveness pathology
Neoplasms immunology
Neoplasms metabolism
Neoplasms therapy
Cancer-Associated Fibroblasts pathology
Neoplasms pathology
Tumor Microenvironment
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 19
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 29883428
- Full Text :
- https://doi.org/10.3390/ijms19051532