Journal
FRONTIERS IN ONCOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2020.01488
Keywords
fibrillar collagens; extracellular matrix; integrins; cancer; metastasis
Categories
Funding
- Fonds de la Recherche Scientifique - FNRS (F.R.S.-FNRS, Belgium)
- Fondation contre le Cancer (foundation of public interest, Belgium)
- Fonds speciaux de la Recherche (University of Liege)
- Fondation Hospitalo Universitaire Leon Fredericq (FHULF, University of Liege)
- Direction Generale Operationnelle de l'Economie, de l'Emploi et de la Recherche from the Service Public de Wallonie (SPW, Belgium)
- Walloon Region through the FRFS-WELBIO strategic research programme
- Wallonia-Brussels Federation (grant for Concerted Research Actions)
- FNRS-Televie grant
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Cancers are complex ecosystems composed of malignant cells embedded in an intricate microenvironment made of different non-transformed cell types and extracellular matrix (ECM) components. The tumor microenvironment is governed by constantly evolving cell-cell and cell-ECM interactions, which are now recognized as key actors in the genesis, progression and treatment of cancer lesions. The ECM is composed of a multitude of fibrous proteins, matricellular-associated proteins, and proteoglycans. This complex structure plays critical roles in cancer progression: it functions as the scaffold for tissues organization and provides biochemical and biomechanical signals that regulate key cancer hallmarks including cell growth, survival, migration, differentiation, angiogenesis, and immune response. Cells sense the biochemical and mechanical properties of the ECM through specialized transmembrane receptors that include integrins, discoidin domain receptors, and syndecans. Advanced stages of several carcinomas are characterized by a desmoplastic reaction characterized by an extensive deposition of fibrillar collagens in the microenvironment. This compact network of fibrillar collagens promotes cancer progression and metastasis, and is associated with low survival rates for cancer patients. In this review, we highlight how fibrillar collagens and their corresponding integrin receptors are modulated during cancer progression. We describe how the deposition and alignment of collagen fibers influence the tumor microenvironment and how fibrillar collagen-binding integrins expressed by cancer and stromal cells critically contribute in cancer hallmarks.
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