Extracellular matrix structure☆
Graphical abstract
Section snippets
Types of extracellular matrices: structure and properties
All tissues and organs contain a mixture of cells and non-cellular components, which form well-organized networks called extracellular matrices (ECMs). The ECMs provide not only physical scaffolds into which cells are embedded but also regulate many cellular processes including growth, migration, differentiation, survival, homeostasis, and morphogenesis [1], [2], [3]. The ECMs consist of a large variety of matrix macromolecules whose precise composition and specific structures vary from tissue
Proteoglycans and hyaluronan
PGs are among the most important structural and functional biomacromolecules in tissues. They consist of a core protein onto which one or more GAG chains of the same or different type are covalently attached. GAGs are long highly negatively charged heteropolysaccharides that contain repeating disaccharides composed mainly of N-acetylated hexosamines (N-acetyl-D-galactosamine or N-acetyl-D-glucosamine) and D-/L-hexuronic acid (D-glucuronic acid or L-iduronic acid). There are six types of
Extracellular matrix proteases
Our view of proteases has come a long way since they were first introduced as generic destructive enzymes associated with protein catabolism and generation of peptides and amino acids during the early stages of protein evolution. The understanding that proteases constitute more than 2% of the total genes in the human genome highlights their contribution in physiological cellular functions as sharp selective scissors, regulating fate, localization, and activity of a variety of proteins,
Extracellular matrix receptors
Apart from the cell surface PGs syndecans and glypicans described above, other ECM receptors include two major receptor families named integrins and DDRs, as well as the HA receptor CD44.
Extracellular matrix targeting: Novel therapeutic approaches
ECM is markedly modified in all pathologies, such as atherosclerosis, autoimmune and inflammatory diseases, and cancer. Nowadays, the microenvironment, in which diseases progress, is thought as equally important as cell populations implicated in the development of the pathologic conditions. For example, healthy microenvironment prevents the cancerous outgrowth of epithelial cells, whereas perturbation of homeostasis enables the initiation and progression of malignancy as well as the emergence
Conclusion
ECM is a complex and dynamic structure that provides the scaffold wherein cells are located. Matrix components encompass multiple, independently folded domains as well as specific glycosylation that provide them with specific sites for interaction. ECM components, such as collagens, PGs, GAGs, elastin, laminin, FN, and matricellular proteins contain various interacting sites with different specificities to matrix components and cell surface receptors, which make them capable to bind with each
Acknowledgments
This research has been co-financed by the European Union (European Social Fund—ESF) and Greek National Funds through the Operational Program “Education and Lifelong Learning” of the National Strategic Reference Framework (NSRF) Research Funding Program: Thales. Investing in knowledge society through the European Social Fund.
References (377)
- et al.
Extracellular matrix signaling in morphogenesis and repair
Curr. Opin. Biotechnol.
(2013) - et al.
The epidermal basement membrane is a composite of separate laminin- or collagen IV-containing networks connected by aggregated perlecan, but not by nidogens
J. Biol. Chem.
(2012) - et al.
The extracellular matrix in development and morphogenesis: a dynamic view
Dev. Biol.
(2010) - et al.
Heparanase: multiple functions in inflammation, diabetes and atherosclerosis
Matrix Biol.
(2013) - et al.
Proteoglycan form and function: a comprehensive nomenclature of proteoglycans
Matrix Biol.
(2015) - et al.
Insights into the key roles of proteoglycans in breast cancer biology and translational medicine
Biochim. Biophys. Acta
(2015) - et al.
Synthesis and assembly of the hyaluronan-containing coats around normal human mesothelial cells
Exp. Cell Res.
(1993) - et al.
Intracellular hyaluronan: a new frontier for inflammation?
Biochim. Biophys. Acta
(2004) Hyaluronan and its binding proteins, the hyaladherins
Curr. Opin. Cell Biol.
(1990)- et al.
Signaling properties of hyaluronan receptors
J. Biol. Chem.
(2002)
Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties
J. Biol. Chem.
Versican and the control of inflammation
Matrix Biol.
Versican and the regulation of cell phenotype in disease
Biochim. Biophys. Acta
Effects of decorin proteoglycan on fibrillogenesis, ultrastructure, and mechanics of type I collagen gels
Matrix Biol.
Decorin expression is important for age-related changes in tendon structure and mechanical properties
Matrix Biol.
Interclass small leucine-rich repeat proteoglycan interactions regulate collagen fibrillogenesis and corneal stromal assembly
Matrix Biol.
Decorin is a biological ligand for the epidermal growth factor receptor
J. Biol. Chem.
Decorin differentially modulates the activity of insulin receptor isoform A ligands
Matrix Biol.
Decorin deficiency promotes hepatic carcinogenesis
Matrix Biol.
Small leucine-rich proteoglycans, at the crossroad of cancer growth and inflammation
Curr. Opin. Genet. Dev.
Cross-talk between estradiol receptor and EGFR/IGF-IR signaling pathways in estrogen-responsive breast cancers: focus on the role and impact of proteoglycans
Matrix Biol.
A decorin-deficient matrix affects skin chondroitin/dermatan sulfate levels and keratinocyte function
Matrix Biol.
Estimation of the binding force of the collagen molecule-decorin core protein complex in collagen fibril
J. Biomech.
Decorin-induced growth suppression is associated with up-regulation of p21, an inhibitor of cyclin-dependent kinases
J. Biol. Chem.
Decorin evokes protracted internalization and degradation of the epidermal growth factor receptor via caveolar endocytosis
J. Biol. Chem.
Sustained down-regulation of the epidermal growth factor receptor by decorin. A mechanism for controlling tumor growth in vivo
J. Biol. Chem.
Decorin antagonizes Met receptor activity and down-regulates {beta}-catenin and Myc levels
J. Biol. Chem.
Decorin antagonizes the angiogenic network: concurrent inhibition of Met, hypoxia inducible factor 1alpha, vascular endothelial growth factor A, and induction of thrombospondin-1 and TIMP3
J. Biol. Chem.
Pivotal role for decorin in angiogenesis
Matrix Biol.
Instructive roles of extracellular matrix on autophagy
Am. J. Pathol.
Biglycan modulates angiogenesis and bone formation during fracture healing
Matrix Biol.
Biglycan, a danger signal that activates the NLRP3 inflammasome via toll-like and P2X receptors
J. Biol. Chem.
The extracellular matrix and inflammation: fibromodulin activates the classical pathway of complement by directly binding C1q
J. Biol. Chem.
Fibromodulin promoted in vitro and in vivo angiogenesis
Biochem. Biophys. Res. Commun.
Identification of beta1 integrin as mediator of melanoma cell adhesion to lumican
Biochem. Biophys. Res. Commun.
Lumican core protein inhibits melanoma cell migration via alterations of focal adhesion complexes
Cancer Lett.
Lumican affects tumor cell functions, tumor-ECM interactions, angiogenesis and inflammatory response
Matrix Biol.
Lumican regulates osteosarcoma cell adhesion by modulating TGFbeta2 activity
Int. J. Biochem. Cell Biol.
Lumican: a new inhibitor of matrix metalloproteinase-14 activity
FEBS Lett.
Endorepellin, a novel inhibitor of angiogenesis derived from the C terminus of perlecan
J. Biol. Chem.
Endorepellin evokes autophagy in endothelial cells
J. Biol. Chem.
Conjugation of LG domains of agrins and perlecan to polymerizing laminin-2 promotes acetylcholine receptor clustering
J. Biol. Chem.
Identification of an agrin mutation that causes congenital myasthenia and affects synapse function
Am. J. Hum. Genet.
The extracellular matrix at a glance
J. Cell Sci.
Extracellular matrix: a functional scaffold
Structure and function of basement membranes
Exp. Biol. Med.
New concepts in basement membrane biology
FEBS J.
Basement membrane proteins: structure, assembly, and cellular interactions
Crit. Rev. Biochem. Mol. Biol.
Heparan sulfate proteoglycans at a glance
J. Cell Sci.
Extracellular matrix molecules: potential targets in pharmacotherapy
Pharmacol. Rev.
Cited by (0)
- ☆
This review is part of the Advanced Drug Delivery Reviews theme issue on “Extracellular Matrix (ECM) and ECM-like materials: Therapeutic Tools and Targets in Cancer Treatment”.