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Current Topics in Developmental Biology 2018The extracellular matrix is a complex network of hydrated macromolecular proteins and sugars that, in concert with bound soluble factors, comprise the acellular stromal... (Review)
Review
The extracellular matrix is a complex network of hydrated macromolecular proteins and sugars that, in concert with bound soluble factors, comprise the acellular stromal microenvironment of tissues. Rather than merely providing structural information to cells, the extracellular matrix plays an instructive role in development and is critical for the maintenance of tissue homeostasis. In this chapter, we review the composition of the extracellular matrix and summarize data illustrating its importance in embryogenesis, tissue-specific development, and stem cell differentiation. We discuss how the biophysical and biochemical properties of the extracellular matrix ligate specific transmembrane receptors to activate intracellular signaling that alter cell shape and cytoskeletal dynamics to modulate cell growth and viability, and direct cell migration and cell fate. We present examples describing how the extracellular matrix functions as a highly complex physical and chemical entity that regulates tissue organization and cell behavior through a dynamic and reciprocal dialogue with the cellular constituents of the tissue. We suggest that the extracellular matrix not only transmits cellular and tissue-level force to shape development and tune cellular activities that are key for coordinated tissue behavior, but that it is itself remodeled such that it temporally evolves to maintain the integrated function of the tissue. Accordingly, we argue that perturbations in extracellular matrix composition and structure compromise key developmental events and tissue homeostasis, and promote disease.
Topics: Animals; Biochemical Phenomena; Cell Differentiation; Cell Lineage; Cell Proliferation; Extracellular Matrix; Humans; Physical Phenomena; Signal Transduction; Stem Cell Niche
PubMed: 29853174
DOI: 10.1016/bs.ctdb.2018.02.002 -
Advanced Healthcare Materials Apr 2019The extracellular matrix (ECM) is a complex and dynamic structural scaffold for cells within tissues and plays an important role in regulating cell function. Recently it... (Review)
Review
The extracellular matrix (ECM) is a complex and dynamic structural scaffold for cells within tissues and plays an important role in regulating cell function. Recently it has become appreciated that the ECM contains bioactive motifs that can directly modulate immune responses. This review describes strategies for engineering immunomodulatory biomaterials that utilize natural ECM-derived molecules and have the potential to harness the immune system for applications ranging from tissue regeneration to drug delivery. A top-down approach utilizes full-length ECM proteins, including collagen, fibrin, or hyaluronic acid-based materials, as well as matrices derived from decellularized tissue. These materials have the benefit of maintaining natural conformation and structure but are often heterogeneous and encumber precise control. By contrast, a bottom-up approach leverages immunomodulatory domains, such as Arg-Gly-Asp (RGD), matrix metalloproteinase (MMP)-sensitive peptides, or leukocyte-associated immunoglobulin-like receptor-1(LAIR-1) ligands, by incorporating them into synthetic materials. These materials have tunable control over immune cell functions and allow for combinatorial approaches. However, the synthetic approach lacks the full natural context of the original ECM protein. These two approaches provide a broad range of engineering techniques for immunomodulation through material interactions and hold the potential for the development of future therapeutic applications.
Topics: Animals; Biocompatible Materials; Cell Line; Extracellular Matrix; Humans; Immunomodulation; Mice; Tissue Engineering
PubMed: 30714328
DOI: 10.1002/adhm.201801578 -
The Journal of Clinical Investigation Jan 2018Intratumoral fibrosis results from the deposition of a cross-linked collagen matrix by cancer-associated fibroblasts (CAFs). This type of fibrosis has been shown to... (Review)
Review
Intratumoral fibrosis results from the deposition of a cross-linked collagen matrix by cancer-associated fibroblasts (CAFs). This type of fibrosis has been shown to exert mechanical forces and create a biochemical milieu that, together, shape intratumoral immunity and influence tumor cell metastatic behavior. In this Review, we present recent evidence that CAFs and tumor cells are regulated by provisional matrix molecules, that metastasis results from a change in the type of stromal collagen cross-link, and that fibrosis and inflammation perpetuate each other through proteolytic and chemotactic mediators released into the tumor stroma. We also discuss aspects of the emerging biology that have potential therapeutic value.
Topics: Animals; Extracellular Matrix; Fibroblasts; Fibrosis; Humans; Neoplasm Metastasis; Neoplasms
PubMed: 29293090
DOI: 10.1172/JCI93554 -
Biomaterials Apr 2016Extracellular matrix (ECM) collectively represents a class of naturally derived proteinaceous biomaterials purified from harvested organs and tissues with increasing... (Review)
Review
Extracellular matrix (ECM) collectively represents a class of naturally derived proteinaceous biomaterials purified from harvested organs and tissues with increasing scientific focus and utility in tissue engineering and repair. This interest stems predominantly from the largely unproven concept that processed ECM biomaterials as natural tissue-derived matrices better integrate with host tissue than purely synthetic biomaterials. Nearly every tissue type has been decellularized and processed for re-use as tissue-derived ECM protein implants and scaffolds. To date, however, little consensus exists for defining ECM compositions or sources that best constitute decellularized biomaterials that might better heal, integrate with host tissues and avoid the foreign body response (FBR). Metrics used to assess ECM performance in biomaterial implants are arbitrary and contextually specific by convention. Few comparisons for in vivo host responses to ECM implants from different sources are published. This review discusses current ECM-derived biomaterials characterization methods including relationships between ECM material compositions from different sources, properties and host tissue response as implants. Relevant preclinical in vivo models are compared along with their associated advantages and limitations, and the current state of various metrics used to define material integration and biocompatibility are discussed. Commonly applied applications of these ECM-derived biomaterials as stand-alone implanted matrices and devices are compared with respect to host tissue responses.
Topics: Animals; Biocompatible Materials; Extracellular Matrix; Extracellular Matrix Proteins; Humans; Tissue Engineering; Tissue Scaffolds
PubMed: 26890039
DOI: 10.1016/j.biomaterials.2016.02.003 -
Cells Apr 2020The extracellular matrix (ECM) is a macromolecules network, in which the most abundant molecule is collagen. This protein in triple helical conformation is highly... (Review)
Review
The extracellular matrix (ECM) is a macromolecules network, in which the most abundant molecule is collagen. This protein in triple helical conformation is highly resistant to proteinases degradation, the only enzymes capable of degrading the collagen are matrix metalloproteinases (MMPs). This resistance and maintenance of collagen, and consequently of ECM, is involved in several biological processes and it must be strictly regulated by endogenous inhibitors (TIMPs). The deregulation of MMPs activity leads to development of numerous diseases. This review shows MMPs complexity.
Topics: Collagen; Extracellular Matrix; Humans; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Proteolysis; Structure-Activity Relationship
PubMed: 32357580
DOI: 10.3390/cells9051076 -
Open Biology Jan 2019During development, both cells and tissues must acquire the correct shape to allow their proper function. This is especially relevant in the nervous system, where the... (Review)
Review
During development, both cells and tissues must acquire the correct shape to allow their proper function. This is especially relevant in the nervous system, where the shape of individual cell processes, such as the axons and dendrites, and the shape of entire tissues, such as the folding of the neocortex, are highly specialized. While many aspects of neural development have been uncovered, there are still several open questions concerning the mechanisms governing cell and tissue shape. In this review, we discuss the role of the extracellular matrix (ECM) in these processes. In particular, we consider how the ECM regulates cell shape, proliferation, differentiation and migration, and more recent work highlighting a key role of ECM in the morphogenesis of neural tissues.
Topics: Animals; Axons; Cell Movement; Cell Proliferation; Cell Shape; Dendrites; Extracellular Matrix; Humans; Models, Neurological; Morphogenesis; Nervous System; Signal Transduction
PubMed: 30958121
DOI: 10.1098/rsob.180216 -
The Journal of Biological Chemistry Mar 2023Although cancer is a genetic disease, physical changes such as stiffening of the extracellular matrix also commonly occur in cancer. Cancer cells sense and respond to... (Review)
Review
Although cancer is a genetic disease, physical changes such as stiffening of the extracellular matrix also commonly occur in cancer. Cancer cells sense and respond to extracellular matrix stiffening through the process of mechanotransduction. Cancer cell mechanotransduction can enhance cancer-promoting cell behaviors such as survival signaling, proliferation, and migration. Glycans, carbohydrate-based polymers, have recently emerged as important mediators and/or modulators of cancer cell mechanotransduction. Stiffer tumors are characterized by increased glycan content on cancer cells and their associated extracellular matrix. Here we review the role of cancer-associated glycans in coupled mechanical and biochemical alterations during cancer progression. We discuss the recent evidence on how increased expression of different glycans, in the form of glycoproteins and proteoglycans, contributes to both mechanical changes in tumors and corresponding cancer cell responses. We conclude with a summary of emerging tools that can be used to modify glycans for future studies in cancer mechanobiology.
Topics: Humans; Biophysics; Extracellular Matrix; Mechanotransduction, Cellular; Neoplasms; Polysaccharides
PubMed: 36693448
DOI: 10.1016/j.jbc.2023.102935 -
Cell Adhesion & Migration 2018The extracellular matrix (ECM) is a master regulator of cellular phenotype and behaviour. It plays a crucial role in both normal tissue homeostasis and complex diseases... (Review)
Review
The extracellular matrix (ECM) is a master regulator of cellular phenotype and behaviour. It plays a crucial role in both normal tissue homeostasis and complex diseases such as cancer. The interplay between the intrinsic factors of cancer cells themselves, including their genotype and signalling networks; and the extrinsic factors of the tumour stroma, such as the ECM and ECM remodelling; together determine the fate and behaviour of cancer cells. As a consequence, tumour progression, metastatic spread and response to therapy are ultimately controlled by ECM-driven fine-tuning of intracellular kinase signalling. The ability to target and uncouple this interaction presents an emerging and promising potential in the treatment of cancer.
Topics: Extracellular Matrix; Homeostasis; Humans; Neoplasm Metastasis; Neoplasms; Signal Transduction; Tumor Microenvironment
PubMed: 29168660
DOI: 10.1080/19336918.2017.1405208 -
Proceedings of the National Academy of... Jan 2022Dormancy is an evolutionarily conserved protective mechanism widely observed in nature. A pathological example is found during cancer metastasis, where cancer cells... (Review)
Review
Dormancy is an evolutionarily conserved protective mechanism widely observed in nature. A pathological example is found during cancer metastasis, where cancer cells disseminate from the primary tumor, home to secondary organs, and enter a growth-arrested state, which could last for decades. Recent studies have pointed toward the microenvironment being heavily involved in inducing, preserving, or ceasing this dormant state, with a strong focus on identifying specific molecular mechanisms and signaling pathways. Increasing evidence now suggests the existence of an interplay between intracellular as well as extracellular biochemical and mechanical cues in guiding such processes. Despite the inherent complexities associated with dormancy, proliferation, and growth of cancer cells and tumor tissues, viewing these phenomena from a physical perspective allows for a more global description, independent from many details of the systems. Building on the analogies between tissues and fluids and thermodynamic phase separation concepts, we classify a number of proposed mechanisms in terms of a thermodynamic metastability of the tumor with respect to growth. This can be governed by interaction with the microenvironment in the form of adherence (wetting) to a substrate or by mechanical confinement of the surrounding extracellular matrix. By drawing parallels with clinical and experimental data, we advance the notion that the local energy minima, or metastable states, emerging in the tissue droplet growth kinetics can be associated with a dormant state. Despite its simplicity, the provided framework captures several aspects associated with cancer dormancy and tumor growth.
Topics: Animals; Extracellular Matrix; Humans; Models, Biological; Neoplasm Metastasis; Neoplasms; Signal Transduction; Tumor Microenvironment
PubMed: 34949715
DOI: 10.1073/pnas.2111046118 -
Reproductive Sciences (Thousand Oaks,... Feb 2013The extracellular matrix (ECM) plays an important role in determining cell and organ function: (1) it is an organizing substrate that provides tissue tensile strength;... (Review)
Review
The extracellular matrix (ECM) plays an important role in determining cell and organ function: (1) it is an organizing substrate that provides tissue tensile strength; (2) it anchors cells and influences cell morphology and function via interaction with cell surface receptors; and (3) it is a reservoir for growth factors. Alterations in the content and the composition of the ECM determine its physical and biological properties, including strength and susceptibility to degradation. The ECM components themselves also harbor cryptic matrikines, which when exposed by conformational change or proteolysis have potent effects on cell function, including stimulating the production of cytokines and matrix metalloproteinases (MMPs). Collectively, these properties of the ECM reflect a dynamic tissue component that influences both tissue form and function. This review illustrates how defects in ECM synthesis and metabolism and the physiological process of ECM turnover contribute to changes in the fetal membranes that precede normal parturition and contribute to the pathological events leading to preterm premature rupture of membranes (PPROM).
Topics: Animals; Extracellular Matrix; Extraembryonic Membranes; Female; Fetal Membranes, Premature Rupture; Humans; Matrix Metalloproteinases; Pregnancy
PubMed: 22267536
DOI: 10.1177/1933719111424454