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European Journal of Cell Biology Apr 2022Metastasis or the progression of malignancy poses a major challenge in cancer therapy and is the principal reason for increased mortality. The epithelial-mesenchymal... (Review)
Review
Metastasis or the progression of malignancy poses a major challenge in cancer therapy and is the principal reason for increased mortality. The epithelial-mesenchymal transition (EMT) of the basement membrane (BM) allows cells of epithelial phenotype to transform into a mesenchymal-like (quasi-mesenchymal) phenotype and metastasize via the lymphovascular system through a metastatic cascade by intravasation and extravasation. This helps in the progression of carcinoma from the primary site to distant organs. Collagen, laminin, and integrin are the prime components of BM and help in tumor cell metastasis, which makes them ideal cancer drug targets. Further, recent studies have shown that collagen, laminin, and integrin can be used as a biomarker for metastatic cells. In this review, we have summarized the current knowledge of such therapeutics, which are either currently in preclinical or clinical stages and could be promising cancer therapeutics. DATA AVAILABILITY: Not applicable.
Topics: Basement Membrane; Collagen; Epithelial-Mesenchymal Transition; Humans; Integrins; Laminin; Membrane Proteins; Neoplasms
PubMed: 35366585
DOI: 10.1016/j.ejcb.2022.151220 -
Nature Jun 2020Tissue sculpting during development has been attributed mainly to cellular events through processes such as convergent extension or apical constriction. However, recent...
Tissue sculpting during development has been attributed mainly to cellular events through processes such as convergent extension or apical constriction. However, recent work has revealed roles for basement membrane remodelling in global tissue morphogenesis. Upon implantation, the epiblast and extraembryonic ectoderm of the mouse embryo become enveloped by a basement membrane. Signalling between the basement membrane and these tissues is critical for cell polarization and the ensuing morphogenesis. However, the mechanical role of the basement membrane in post-implantation embryogenesis remains unknown. Here we demonstrate the importance of spatiotemporally regulated basement membrane remodelling during early embryonic development. Specifically, we show that Nodal signalling directs the generation and dynamic distribution of perforations in the basement membrane by regulating the expression of matrix metalloproteinases. This basement membrane remodelling facilitates embryo growth before gastrulation. The establishment of the anterior-posterior axis further regulates basement membrane remodelling by localizing Nodal signalling-and therefore the activity of matrix metalloproteinases and basement membrane perforations-to the posterior side of the embryo. Perforations on the posterior side are essential for primitive-streak extension during gastrulation by rendering the basement membrane of the prospective primitive streak more prone to breaching. Thus spatiotemporally regulated basement membrane remodelling contributes to the coordination of embryo growth, morphogenesis and gastrulation.
Topics: Animals; Basement Membrane; Blastocyst; Embryo, Mammalian; Embryonic Development; Extracellular Matrix; Female; Gastrula; Male; Matrix Metalloproteinases; Mice; Nodal Signaling Ligands; Primitive Streak
PubMed: 32523119
DOI: 10.1038/s41586-020-2264-2 -
Stroke Apr 2020
Review
Topics: Animals; Basement Membrane; Blood-Brain Barrier; Brain Ischemia; Humans; Proteoglycans; Stroke
PubMed: 32122290
DOI: 10.1161/STROKEAHA.120.028928 -
The Journal of Investigative Dermatology Jun 1990Fibronectins are widespread extracellular matrix and body fluid glycoproteins, capable of multiple interactions with cell surfaces and other matrix components. Their... (Review)
Review
Fibronectins are widespread extracellular matrix and body fluid glycoproteins, capable of multiple interactions with cell surfaces and other matrix components. Their structure at a molecular level has been resolved, yet there are still many unanswered questions regarding their biologic activity in vivo. Much data suggests that fibronectins may promote extracellular matrix assembly, and cell adhesion to those matrices. However, one outstanding enigma is that fibronectins may, under different circumstances, promote both cell migration and anchorage. An analysis of the interaction of fibroblasts with proteolytically derived and purified domains of plasma fibronectin revealed that the type of adhesion and the correlated cytoskeletal organization depended on multiple interactions of fibronectin domains with the cell surface. Human dermal fibroblasts were capable of interacting with the integrin-binding domain and both heparin-binding domains of the plasma fibronectin molecule and their interactions determined the type of adhesion. The same principle was seen in a study of the ability of plasma fibronectin to promote basement membrane assembly in an endodermal cell line, PF-HR9. There also, interactions of both heparin- and integrin-binding domains combined to promote the deposition of a proteoglycan, laminin, and type IV collagen-containing basement membrane matrix. The underlying conclusion from our studies is, therefore, that fibronectins may, through their different isotypes, multiple receptors, and varying interaction of one or more domains with those receptors, result in a spectrum of responses in different cell types. The molecular details of this array of biologic activities is not resolved but is the target of much current research.
Topics: Animals; Basement Membrane; Cell Adhesion; Cytoskeleton; Fibronectins; Humans; Skin
PubMed: 2191056
DOI: 10.1111/1523-1747.ep12874973 -
The Journal of Cell Biology Aug 2019In epithelial cancers, cells must invade through basement membranes (BMs) to metastasize. The BM, a thin layer of extracellular matrix underlying epithelial and... (Review)
Review
In epithelial cancers, cells must invade through basement membranes (BMs) to metastasize. The BM, a thin layer of extracellular matrix underlying epithelial and endothelial tissues, is primarily composed of laminin and collagen IV and serves as a structural barrier to cancer cell invasion, intravasation, and extravasation. BM invasion has been thought to require protease degradation since cells, which are typically on the order of 10 µm in size, are too large to squeeze through the nanometer-scale pores of the BM. However, recent studies point toward a more complex picture, with physical forces generated by cancer cells facilitating protease-independent BM invasion. Moreover, collective cell interactions, proliferation, cancer-associated fibroblasts, myoepithelial cells, and immune cells are all implicated in regulating BM invasion through physical forces. A comprehensive understanding of BM structure and mechanics and diverse modes of BM invasion may yield new strategies for blocking cancer progression and metastasis.
Topics: Animals; Basement Membrane; Biomechanical Phenomena; Cell Communication; Humans; Neoplasm Invasiveness; Neoplasms; Peptide Hydrolases
PubMed: 31315943
DOI: 10.1083/jcb.201903066 -
Cell and Tissue Research Dec 2018Basement membranes are thin connective tissue structures composed of organ-specific assemblages of collagens, laminins, proteoglycan-like perlecan, nidogens, and other... (Review)
Review
Basement membranes are thin connective tissue structures composed of organ-specific assemblages of collagens, laminins, proteoglycan-like perlecan, nidogens, and other components. Traditionally, basement membranes are thought of as structures which primarily function to anchor epithelial, endothelial, or parenchymal cells to underlying connective tissues. While this role is important, other functions such as the modulation of growth factors and cytokines that regulate cell proliferation, migration, differentiation, and fibrosis are equally important. An example of this is the critical role of both the epithelial basement membrane and Descemet's basement membrane in the cornea in modulating myofibroblast development and fibrosis, as well as myofibroblast apoptosis and the resolution of fibrosis. This article compares the ultrastructure and functions of key basement membranes in several organs to illustrate the variability and importance of these structures in organs that commonly develop fibrosis.
Topics: Animals; Basement Membrane; Cornea; Fibrosis; Humans; Organ Specificity; Regeneration
PubMed: 30284084
DOI: 10.1007/s00441-018-2934-7 -
Matrix Biology : Journal of the... Jan 2019Basement membrane plays a foundational role in the structure and maintenance of many tissues throughout the animal kingdom. In addition to signaling to cells through... (Review)
Review
Basement membrane plays a foundational role in the structure and maintenance of many tissues throughout the animal kingdom. In addition to signaling to cells through cell-surface receptors, basement membrane directly influences the development and maintenance of organ shape via its mechanical properties. The mechanical properties of basement membrane are dictated by its composition, geometry, and crosslinking. Distinguishing between the ways the basement membrane influences morphology in vivo poses a major challenge. Drosophila melanogaster, already established as a powerful model for the analysis of cell signaling, has in recent years emerged as a tractable model for understanding the roles of basement membrane stiffness in vivo, in shaping and maintaining the morphology of tissues and organs. In addition to the plethora of genetic tools available in flies, the major proteins found in vertebrate basement membranes are all present in Drosophila. Furthermore, Drosophila has fewer copies of the genes encoding these proteins, making flies more amenable to genetic manipulation than vertebrate models. Because the development of Drosophila organs has been well-characterized, these different organ systems offer a variety of contexts for analyzing the role of basement membrane in development. The developing egg chamber and central nervous system, for example, have been important models for assessing the role of basement membrane stiffness in influencing organ shape. Studies in the nervous system have also shown how basement membrane stiffness can influence cellular migration in vivo. Finally, work in the imaginal wing disc has illuminated a distinct mechanism by which basement membrane can alter organ shape and size, by sequestering signaling ligands. This mini-review highlights the recent discoveries pertaining to basement membrane mechanics during Drosophila development.
Topics: Animals; Basement Membrane; Cell Movement; Drosophila melanogaster; Nervous System; Organogenesis; Ovum; Receptors, Cell Surface; Signal Transduction
PubMed: 29656148
DOI: 10.1016/j.matbio.2018.04.004 -
Cell Cycle (Georgetown, Tex.) 2015The vascular basement membrane (BM) is a thin and dense cross-linked extracellular matrix layer that covers and protects blood vessels. Understanding how cells cross the... (Review)
Review
The vascular basement membrane (BM) is a thin and dense cross-linked extracellular matrix layer that covers and protects blood vessels. Understanding how cells cross the physical barrier of the vascular BM will provide greater insight into the potentially critical role of vascular BM breaching in cancer extravasation, leukocyte trafficking and angiogenic sprouting. In the last year, new evidence has mechanistically linked the breaching of vascular BM with the formation of specific cellular micro-domains known as podosomes and invadopodia. These structures are specialized cell-matrix contacts with an inherent ability to degrade the extracellular matrix. Specifically, the formation of podosomes or invadopodia was shown as an important step in vascular sprouting and tumor cell extravasation, respectively. Here, we review and comment on these recent findings and explore the functions of podosomes and invadopodia within the context of pathological processes such as tumor dissemination and tumor angiogenesis.
Topics: Angiogenic Proteins; Animals; Basement Membrane; Blood Vessels; Cell Movement; Extracellular Matrix Proteins; Humans; Neoplasm Invasiveness; Neoplasms; Neovascularization, Pathologic; Podosomes
PubMed: 25789660
DOI: 10.1080/15384101.2015.1026523 -
Cellular and Molecular Life Sciences :... Feb 2022In the cornea, the epithelial basement membrane (EBM) and corneal endothelial Descemet's basement membrane (DBM) critically regulate the localization, availability and,... (Review)
Review
In the cornea, the epithelial basement membrane (EBM) and corneal endothelial Descemet's basement membrane (DBM) critically regulate the localization, availability and, therefore, the functions of transforming growth factor (TGF)β1, TGFβ2, and platelet-derived growth factors (PDGF) that modulate myofibroblast development. Defective regeneration of the EBM, and notably diminished perlecan incorporation, occurs via several mechanisms and results in excessive and prolonged penetration of pro-fibrotic growth factors into the stroma. These growth factors drive mature myofibroblast development from both corneal fibroblasts and bone marrow-derived fibrocytes, and then the persistence of these myofibroblasts and the disordered collagens and other matrix materials they produce to generate stromal scarring fibrosis. Corneal stromal fibrosis often resolves completely if the inciting factor is removed and the BM regenerates. Similar defects in BM regeneration are likely associated with the development of fibrosis in other organs where perlecan has a critical role in the modulation of signaling by TGFβ1 and TGFβ2. Other BM components, such as collagen type IV and collagen type XIII, are also critical regulators of TGF beta (and other growth factors) in the cornea and other organs. After injury, BM components are dynamically secreted and assembled through the cooperation of neighboring cells-for example, the epithelial cells and keratocytes for the corneal EBM and corneal endothelial cells and keratocytes for the corneal DBM. One of the most critical functions of these reassembled BMs in all organs is to modulate the pro-fibrotic effects of TGFβs, PDGFs and other growth factors between tissues that comprise the organ.
Topics: Animals; Basement Membrane; Corneal Diseases; Fibrosis; Heparan Sulfate Proteoglycans; Humans; Transforming Growth Factor beta
PubMed: 35188596
DOI: 10.1007/s00018-022-04184-7 -
Investigative Ophthalmology & Visual... Sep 2013The corneal epithelial basement membrane (BM) is positioned between basal epithelial cells and the stroma. This highly specialized extracellular matrix functions not... (Review)
Review
The corneal epithelial basement membrane (BM) is positioned between basal epithelial cells and the stroma. This highly specialized extracellular matrix functions not only to anchor epithelial cells to the stroma and provide scaffolding during embryonic development but also during migration, differentiation, and maintenance of the differentiated epithelial phenotype. Basement membranes are composed of a diverse assemblage of extracellular molecules, some of which are likely specific to the tissue where they function; but in general they are composed of four primary components--collagens, laminins, heparan sulfate proteoglycans, and nidogens--in addition to other components such as thrombospondin-1, matrilin-2, and matrilin-4 and even fibronectin in some BM. Many studies have focused on characterizing BM due to their potential roles in normal tissue function and disease, and these structures have been well characterized in many tissues. Comparatively few studies, however, have focused on the function of the epithelial BM in corneal physiology. Since the normal corneal stroma is avascular and has relatively low keratocyte density, it is expected that the corneal BM would be different from the BM in other tissues. One function that appears critical in homeostasis and wound healing is the barrier function to penetration of cytokines from the epithelium to stroma (such as transforming growth factor β-1), and possibly from stroma to epithelium (such as keratinocyte growth factor). The corneal epithelial BM is also involved in many inherited and acquired corneal diseases. This review examines this structure in detail and discusses the importance of corneal epithelial BM in homeostasis, wound healing, and disease.
Topics: Animals; Basement Membrane; Corneal Diseases; Epithelium, Corneal; Humans
PubMed: 24078382
DOI: 10.1167/iovs.13-12547