Abstract
The extracellular matrix is a structure composed of many molecules, including fibrillar (types I, II, III, V, XI, XXIV, XXVII) and non-fibrillar collagens (mainly basement membrane collagens: types IV, VIII, X), non-collagenous glycoproteins (elastin, laminin, fibronectin, thrombospondin, tenascin, osteopontin, osteonectin, entactin, periostin) embedded in a gel of negatively charged water-retaining glycosaminoglycans (GAGs) such as non-sulfated hyaluronic acid (HA) and sulfated GAGs which are linked to a core protein to form proteoglycans (PGs). This highly dynamic molecular network provides critical biochemical and biomechanical cues that mediate the cell–cell and cell–matrix interactions, influence cell growth, migration and differentiation and serve as a reservoir of cytokines and growth factors’ action. The breakdown of normal ECM and its replacement with tumor ECM modulate the tumor microenvironment (TME) composition and is an essential part of tumorigenesis and metastasis, acting as key driver for malignant progression. Abnormal ECM also deregulate behavior of stromal cells as well as facilitating tumor-associated angiogenesis and inflammation. Thus, the tumor matrix modulates each of the classically defined hallmarks of cancer promoting the growth, survival and invasion of the cancer. Moreover, various ECM-derived components modulate the immune response affecting T cells, tumor-associated macrophages (TAM), dendritic cells and cancer-associated fibroblasts (CAF). This review article considers the role that extracellular matrix play in breast cancer. Determining the detailed connections between the ECM and cellular processes has helped to identify novel disease markers and therapeutic targets.
Highlights
Female breast cancer is the leading cause of global cancer incidence, with an estimated2.3 million women diagnosed with breast cancer and 685,000 deaths globally
It is assumed that collagen binding triggers structural reorganization of DDR2 surface loops, which leads to an activation of discoidin domains, and it is worth highlighting that mentioned domains can independently bind to collagen or simultaneous binding of two domains to the protein triple helix can occur [21,40]
An essential role in providing and maintaining the characteristic mechanical properties of elastin is attributed to the extensive cross-linking of tropoelastin, which is catalyzed by lysyl oxidase (LOX) [10,13,47,49]
Summary
Female breast cancer is the leading cause of global cancer incidence, with an estimated. These, in turn, are divided into smaller elements called lobules [2,6] These lobes and lobules are connected via milk ducts. The extracellular matrix (ECM), which is a perfectly organized and efficiently managed structure, is formed from a great variety of macromolecules, forming a multitude of combinations, depending on the tissue in which this structure occurs It can be regarded as a physical scaffold for cellular components, the range of functions it performs is much broader, and many of them are not, as yet, believed to be known and described. The composition of the ECM in a given tissue is determined during its development by a biochemical dialogue between the cells and the environment This composition is an expression of its adaptation to the function performed in the body [10–15].
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