Abstract
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.
Highlights
Cancer progression is a highly dynamic process implicating distinct features responsible for tumor growth and metastatic dissemination
In order to complete this overview of the roles of fibrillar collagens in cancer, we explored in silico, whether the mRNA level of the different fibrillar collagens were connected with clinical outcome in human cancers
Even if the hallmarks of cancer are driven by oncogenic mutations, most of them are modulated by the biochemical and biomechanical properties of the extracellular matrix (ECM) that surrounds the tumor
Summary
Cancer progression is a highly dynamic process implicating distinct features responsible for tumor growth and metastatic dissemination. Solid tumor’s ECM is typically more rigid than normal tissue as a result of the overexpression of several ECM components, including collagens I, II, III, V, IX, XI, and heparan sulfate proteoglycans as well as ECM-crosslinking enzymes such as lysyl oxidases [21, 22] This accumulation generates a stroma characterized by a dense meshwork of fibrillar proteins (Figure 1), which progressively causes tissue stiffening, a hallmark of many cancers, such as breast, pancreatic and prostate cancers [23, 24]. Type I collagen represents the archetypal fibrillar collagen due to the presence of a trimeric structure and the absence of imperfection in the triple helix This molecular organization contrasts with that of other collagen families, which present interruptions in the triple helix or do not assemble into fibrils (Figure 3). Type I collagen is mostly incorporated into a composite containing either type
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