Abstract
In recent years, it has become increasingly evident that cancer cells and the local microenvironment are crucial in the development and progression of tumors. One of the major components of the tumor microenvironment is the extracellular matrix (ECM), which comprises a complex mixture of components, including proteins, glycoproteins, proteoglycans, and polysaccharides. In addition to providing structural and biochemical support to tumor tissue, the ECM undergoes remodeling that alters the biochemical and mechanical properties of the tumor microenvironment and contributes to tumor progression and resistance to therapy. A novel concept has emerged, in which tumor-driven ECM remodeling affects the release of ECM components into peripheral blood, the levels of which are potential diagnostic or prognostic markers for tumors. This review discusses the most recent evidence on ECM remodeling-derived signals that are detectable in the bloodstream, as new early diagnostic and risk prediction tools for the most frequent solid cancers.
Highlights
Solid tumors are complex entities that are characterized by the coexistence of cancer cells and their microenvironment, composed of various cell types, including fibroblasts, adipocytes, endothelial cells, bone marrow-derived immune cells, and the extracellular matrix (ECM) [1]
Levels of collagen 10 differed significantly only in females, whereas secreted protein acidic and rich in cysteine (SPARC) maintained significant differences between gender subgroups, with good overall discrimination of patients from controls. Osteopontin, another protein that has been implicated in tissue remodeling, is significantly higher in serum from patients with lung cancer compared with healthy volunteers, and when smoking history was considered, the levels of circulating osteopontin were higher in smokers than in nonsmoking and ex-smoking lung cancer patients [31], suggesting that smoking status is an important parameter that must be taken into account when searching for new lung cancer biomarkers
A panel of matrix metalloproteinases (MMPs) was analyzed in serum from Pancreatic cancer (PC) patients—MMP-1, MMP-3, MMP-7, MMP-9, MMP-10, and MMP-12 were higher in cancer patients compared with healthy donors, showing good diagnostic accuracy, of which MMP-7 and MMP-12 achieved perfect discrimination [45]
Summary
Solid tumors are complex entities that are characterized by the coexistence of cancer cells and their microenvironment, composed of various cell types, including fibroblasts, adipocytes, endothelial cells, bone marrow-derived immune cells, and the extracellular matrix (ECM) [1] All of these elements contribute to the development of cancer, which is not an entirely cancer cell-autonomous process but depends on the ability of cellular and noncellular components in the microenvironment to: i) establish a pro-tumor milieu, ii) regulate tumor cell behavior, and iii) coevolve with cancer cells [2,3]. The ECM is a complex network of noncellular components, including structural proteins—predominantly collagens—, matricellular proteins—e.g., periostin, thrombospondins, osteopontin and secreted protein acidic and rich in cysteine (SPARC)—, glycoproteins, proteoglycans, and polysaccharides These molecules contribute in deposition and arrangement of ECM and modulate cell-matrix interaction through their distinct biochemical and physical properties. We discuss the results that have been obtained in the past 10 years of cancer research on the potential function of circulating ECM remodeling-derived molecules in the diagnosis and prognosis of solid tumors
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