Collagen biology making inroads into prognosis and treatment of cancer progression and metastasis
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Collagen biology making inroads into prognosis and treatment of cancer progression and metastasis Ana C. Martins Cavaco 1 & Sara Dâmaso 2 & Sandra Casimiro 1 & Luís Costa 1,2
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Progression through dissemination to tumor-surrounding tissues and metastasis development is a hallmark of cancer that requires continuous cell-to-cell interactions and tissue remodeling. In fact, metastization can be regarded as a tissue disease orchestrated by cancer cells, leading to neoplastic colonization of new organs. Collagen is a major component of the extracellular matrix (ECM), and increasing evidence suggests that it has an important role in cancer progression and metastasis. Desmoplasia and collagen biomarkers have been associated with relapse and death in cancer patients. Despite the increasing interest in ECM and in the desmoplastic process in tumor microenvironment as prognostic factors and therapeutic targets in cancer, further research is required for a better understanding of these aspects of cancer biology. In this review, published evidence correlating collagen with cancer prognosis is retrieved and analyzed, and the role of collagen and its fragments in cancer pathophysiology is discussed. Keywords Cancer . Desmoplasia . Collagen . Collagen fragments . Biologic functions . Prognostic tools
1 Collagen, a dynamic and continuously remodeling ECM protein The extracellular matrix (ECM) has been defined as the noncellular structural support of tissues. It is physiologically active and responsible for cell–cell communication, cell adhesion, and cell proliferation [1]. In vitro, anchoring substrates are crucial for viability of most animal cells, which survive by protruding, adhering, and spatially interacting with the surrounding ECM through various membrane adhesion receptors [2, 3]. Furthermore, cells can sense and transduce ECM mechanical rigidity to coordinate morphological organization and signaling events that modulate gene expression [4]. During tissue development, biophysical and biochemical feedback from tissue microenvironment is sensed by tissue resident cells and dictates, which ECM components are produced, deposited, and Ana C. Martins Cavaco and Sara Dâmaso contributed equally to this work. * Luís Costa [email protected] 1
Luis Costa Lab, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal
2
Serviço de Oncologia, Hospital de Santa Maria-CHULN, 1649-028 Lisboa, Portugal
arranged by those cells [5]. Collagen, proteoglycans, laminin, and fibronectin are the main ECM components. In this review, the authors focus on collagen superfamily members that are altered during tumorigenesis.
1.1 Collagens exhibit common structural traits Collagen is one of the main ECM components and the most abundant protein in human tissue, with 28 subtypes identified in vertebrates to date [6]. Collagens can be organized into subgroups according to their physiological location within tissues—
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