scholarly journals Vascular cell-matrix adhesion in development and cancer

2021 ◽  
Author(s):  
Christina Arapatzi ◽  
Georgia Rouni ◽  
Vassiliki Kostourou
Keyword(s):  
Endothelial Cells ◽  
Molecular Mechanisms ◽  
Notch Signalling ◽  
Tumour Angiogenesis ◽  
Genetic Studies ◽  
Cell Matrix ◽  
Vascular Morphogenesis ◽  
Current State ◽  
Cell Matrix Adhesion

The development and homeostasis of vertebrate organisms depend on the “tree of life”, that is the intricate network of vascular tubes composed by endothelial cells attached to the basement membrane and surrounded by perivascular cells. Although many studies have revealed the fundamental role of cytokines, growth factors and Notch signalling in vascular morphogenesis, we still lack sufficient understanding of the molecular mechanisms controlling the various steps of the angiogenic processes. Emerging data highlight that cell adhesions are key players in vascular morphogenesis. In this review, we focus on endothelial cells and we present the current state of knowledge regarding the role of cell-matrix adhesions in developmental and tumour angiogenesis, attained mainly from genetic studies and animal models.

Podokinesis in endothelial cell migration: role of nitric oxide

1998 ◽  
Vol 274 (1) ◽  
pp. C236-C244 ◽  
Author(s):  
Eisei Noiri ◽  
Eugene Lee ◽  
Jacqueline Testa ◽  
James Quigley ◽  
David Colflesh ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Endothelial Cell ◽  
No Synthase ◽  
Endothelial Cell Migration ◽  
Guidance Cues ◽  
Cell Matrix ◽  
Cell Matrix Adhesion

Previously, we demonstrated the role of nitric oxide (NO) in transforming epithelial cells from a stationary to locomoting phenotype [E. Noiri, T. Peresleni, N. Srivastava, P. Weber, W. F. Bahou, N. Peunova, and M. S. Goligorsky. Am. J. Physiol. 270 ( Cell Physiol. 39): C794–C802, 1996] and its permissive function in endothelin-1-stimulated endothelial cell migration (E. Noiri, Y. Hu, W. F. Bahou, C. Keese, I. Giaever, and M. S. Goligorsky. J. Biol. Chem. 272: 1747–1753, 1997). In the present study, the role of functional NO synthase in executing the vascular endothelial growth factor (VEGF)-guided program of endothelial cell migration and angiogenesis was studied in two independent experimental settings. First, VEGF, shown to stimulate NO release from simian virus 40-immortalized microvascular endothelial cells, induced endothelial cell transwell migration, whereas N G-nitro-l-arginine methyl ester (l-NAME) or antisense oligonucleotides to endothelial NO synthase suppressed this effect of VEGF. Second, in a series of experiments on endothelial cell wound healing, the rate of VEGF-stimulated cell migration was significantly blunted by the inhibition of NO synthesis. To gain insight into the possible mode of NO action, we next addressed the possibility that NO modulates cell matrix adhesion by performing impedance analysis of endothelial cell monolayers subjected to NO. The data showed the presence of spontaneous fluctuations of the resistance in ostensibly stationary endothelial cells. Spontaneous oscillations were induced by NO, which also inhibited cell matrix adhesion. This process we propose to term “podokinesis” to emphasize a scalar form of micromotion that, in the presence of guidance cues, e.g., VEGF, is transformed to a vectorial movement. In conclusion, execution of the program for directional endothelial cell migration requires two coexisting messages: NO-induced podokinesis (scalar motion) and guidance cues, e.g., VEGF, which imparts a vectorial component to the movement. Such a requirement for the dual signaling may explain a mismatch in the demand and supply with newly formed vessels in different pathological states accompanied by the inhibition of NO synthase.

scholarly journals The role of Notch ligand, Delta-like ligand 4 (DLL4), in cancer angiogenesis—implications for therapy

2021 ◽  
Author(s):  
Marlena Brzozowa-Zasada
Keyword(s):  
Cancer Therapy ◽  
Notch Signalling ◽  
Signalling Pathway ◽  
Gamma Secretase ◽  
Tumour Angiogenesis ◽  
Notch Signalling Pathway ◽  
Expression Levels ◽  
Blocking Agents ◽  
Anti Cancer

Summary Background It is generally accepted that angiogenesis is a complex and tightly regulated process characterized by the growth of blood vessels from existing vasculature. Activation of the Notch signalling pathway affects multiple aspects of vascular development. One of the components of the Notch signalling pathway, Delta-like ligand 4 (DLL4), has recently appeared as a critical regulator of tumour angiogenesis and thus as a promising therapeutic target. Methods This review article includes available data from peer-reviewed publications associated with the role of DLL4 in cancer angiogenesis. Searches were performed in PubMed, EMBASE, Google Scholar and Web of Science using the terms “tumour angiogenesis”, “DLL4”, “Notch signalling” and “anti-cancer therapy”. Results The survival curves of cancer patients revealed that the patients with high DLL4 expression levels had significantly shorter survival times than the patients with low DLL4 expression. Moreover, a positive correlation was also identified between DLL4 and VEGF receptorsʼ expression levels. It seems that inhibition of DLL4 may exert potent growth inhibitory effects on some tumours resistant to anti-VEGF therapies. A great number of blocking agents of DLL4/Notch signalling including anti-DLL4 antibodies, DNA vaccination, Notch antibodies and gamma-secretase inhibitors have been studied in preclinical tumour models. Conclusion DLL4 seems to be a promising target in anti-cancer therapy. Nevertheless, the careful evaluation of adverse effects on normal physiological processes in relation to therapeutic doses of anti-DLL4 drugs will be significant for advancement of DLL4 blocking agents in clinical oncology.

scholarly journals Interaction between Galectin-3 and Integrins Mediates Cell-Matrix Adhesion in Endothelial Cells and Mesenchymal Stem Cells

2021 ◽  
Vol 22 (10) ◽  
pp. 5144
Author(s):  
Antonín Sedlář ◽  
Martina Trávníčková ◽  
Pavla Bojarová ◽  
Miluše Vlachová ◽  
Kristýna Slámová ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Cell Adhesion ◽  
Vascular Tissue ◽  
Cell Functions ◽  
Matrix Adhesion ◽  
Cell Matrix ◽  
Selective Ligand ◽  
Galectin 3 ◽  
Cell Matrix Adhesion

Galectin-3 (Gal-3) is a β-galactoside-binding protein that influences various cell functions, including cell adhesion. We focused on the role of Gal-3 as an extracellular ligand mediating cell-matrix adhesion. We used human adipose tissue-derived stem cells and human umbilical vein endothelial cells that are promising for vascular tissue engineering. We found that these cells naturally contained Gal-3 on their surface and inside the cells. Moreover, they were able to associate with exogenous Gal-3 added to the culture medium. This association was reduced with a β-galactoside LacdiNAc (GalNAcβ1,4GlcNAc), a selective ligand of Gal-3, which binds to the carbohydrate recognition domain (CRD) in the Gal-3 molecule. This ligand was also able to detach Gal-3 newly associated with cells but not Gal-3 naturally present on cells. In addition, Gal-3 preadsorbed on plastic surfaces acted as an adhesion ligand for both cell types, and the cell adhesion was resistant to blocking with LacdiNAc. This result suggests that the adhesion was mediated by a binding site different from the CRD. The blocking of integrin adhesion receptors on cells with specific antibodies revealed that the cell adhesion to the preadsorbed Gal-3 was mediated, at least partially, by β1 and αV integrins—namely α5β1, αVβ3, and αVβ1 integrins.

Matrix metalloproteinase-9 : surrogate marker and therapeutic target against neurovascular impairment after cerebral ischemia

2015 ◽  
Author(s):  
◽  
Shanyan Chen
Keyword(s):  
Endothelial Cells ◽  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Molecular Mechanisms ◽  
Combined Treatment ◽  
Cell Penetrating Peptides ◽  
Therapeutic Window ◽  
Gelatinase Activity

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Stroke ranks fourth among all causes of death, and acute ischemic stroke is the most common form. The neurovascular unit (NVU) describes a basic functional structure in the brain and is primarily composed of endothelial cells, pericytes, astrocytes, microglia and neurons. The dynamic structure of the NVU is highly regulated due to interactions between different cells and extracellular matrix (ECM) components. Proteolysis of the ECM by matrix metalloproteinases (MMPs), especially MMP-9, plays an important role in the pathophysiology of cerebral ischemia and administration of tissue plasminogen activator (tPA). The activation of gelatinases (MMP-2/9) is considered a key mechanism involved in the impairment of NVU. The overall goal of this research project is to examine the role of MMP-9 in the neurovascular impairment after ischemic stroke in mice. In this project, we implemented a new strategy using gelatinase-activatable cell-penetrating peptides (ACPPs) tagged with fluorescence and/or gadolinium-based contrast agents to investigate proteolysis of gelatinases as surrogate markers of neurovascular integrity. We presented evidence that the combination of a sensitive fluorescent chromatophore and MRI contrast enhancement agent can be used to monitor gelatinase activity and its distribution in cultured neurons as well as in mice after focal cerebral ischemia. Detection of the activity of gelatinases in vivo using ACPPs could provide insights into the underlying mechanism for gelatinase proteolysis that mediate ischemia-related neurovascular impairment. We also applied a two-dimensional (2D) gelatin zymography technique that combines isoelectric focusing (IEF) with zymographic electrophoresis. We demonstrated that the 2D zymography approach can improve separation of different isoforms of gelatinases in both in vitro and in vivo conditions. 2D zymography is an effective method to separate posttranslational modification isoforms of gelatinases and to identify modifications that regulate their enzymatic activity in acute brain injuries. In work that follows, we used a fibrin-rich blood clot to occlude the middle cerebral artery (MCA) in mice as a model to represent the critical thromboembolic features of ischemic stroke in humans. In this study, we evaluated effects of SB-3CT, a mechanism-based inhibitor selective for gelatinases. We demonstrated MMP-9 activation and neurovasculature impairment in this stroke model, and showed the ability of SB-3CT to inhibit MMP-9 activity in vivo, which in turn resulted in maintenance of laminin, antagonism of pericyte contraction and loss, preservation of laminin-positive pericytes and endothelial cells, and thus rescuing neurons from apoptosis and preventing intracerebral hemorrhage. We further demonstrated that SB-3CT/tPA combined treatment could attenuate MMP-9 -- mediated degradation of endothelial laminin, impairment of endothelial cells, and decrease of caveolae -- mediated transcytosis. Early inhibition of MMP-9 proteolysis by SB-3CT decreased brain damage, reduced BBB disruption, and prevented hemorrhagic transformation after delayed tPA treatment. Therefore usage of SB-3CT will be helpful in accessing combination therapy with tPA in ischemic stroke. Results from these studies indicate the important role of MMP-9 in cerebral ischemia and thus the need for further studies to explore the molecular mechanisms underlying its activation and regulation. Results further demonstrated that the combined use of MMP-9 inhibitor with tPA may extend tPA therapeutic window for mitigating stroke damage.

scholarly journals IL-17B Can Impact on Endothelial Cellular Traits Linked to Tumour Angiogenesis

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Andrew J. Sanders ◽  
Xiaoxia Guo ◽  
Malcolm D. Mason ◽  
Wen G. Jiang
Keyword(s):  
Rheumatoid Arthritis ◽  
Endothelial Cell ◽  
Inflammatory Response ◽  
Cellular Migration ◽  
Tumour Angiogenesis ◽  
Tubule Formation ◽  
Founding Member ◽  
Cell Matrix ◽  
Cell Matrix Adhesion

IL-17B is a member of the IL-17 cytokine family which have been implicated in inflammatory response and autoimmune diseases such as rheumatoid arthritis. The founding member of this family, IL-17 (or IL-17A), has also been implicated in promoting tumour angiogenesis through the induction of other proangiogenic factors. Here we examine the potential of recombinant human IL-17B to contribute to the angiogenic process. In vitro rhIL-17B was able to inhibit HECV endothelial cell-matrix adhesion and cellular migration and also, at higher concentrations, could substantially reduce tubule formation compared to untreated HECV cells in a Matrigel tubule formation assay. This data suggests that IL-17B may act in an antiangiogenic manner.

scholarly journals Revealing the role of phospholipase Cβ3 in the regulation of VEGF-induced vascular permeability

Blood ◽  
2012 ◽  
Vol 120 (11) ◽  
pp. 2167-2173 ◽  
Author(s):  
Luke H. Hoeppner ◽  
Kathryn N. Phoenix ◽  
Karl J. Clark ◽  
Resham Bhattacharya ◽  
Xun Gong ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Real Time ◽  
Molecular Mechanisms ◽  
Negative Regulator ◽  
Transgenic Zebrafish ◽  
Genetic Studies ◽  
In Vivo Models ◽  
Ischemic Diseases

AbstractVEGF induces vascular permeability (VP) in ischemic diseases and cancer, leading to many pathophysiological consequences. The molecular mechanisms by which VEGF acts to induce hyperpermeability are poorly understood and in vivo models that easily facilitate real-time, genetic studies of VP do not exist. In the present study, we report a heat-inducible VEGF transgenic zebrafish (Danio rerio) model through which VP can be monitored in real time. Using this approach with morpholino-mediated gene knock-down and knockout mice, we describe a novel role of phospholipase Cβ3 as a negative regulator of VEGF-mediated VP by regulating intracellular Ca2+ release. Our results suggest an important effect of PLCβ3 on VP and provide a new model with which to identify genetic regulators of VP crucial to several disease processes.

The importance of epigenome research in the diagnosis and treatment of endometriosis

2018 ◽  
Vol 86 (4) ◽  
pp. 325
Author(s):  
Przemysław Krzysztof Wirstlein ◽  
Paweł P. Jagodziński ◽  
Małgorzata Szczepańska
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Diagnosis And Treatment ◽  
Control Of Gene Expression ◽  
Epigenetic Control ◽  
Current State

The causes of endometriosis remain unexplained. Studying the molecular mechanisms at the origin of the lesions leads to conclusions about the important role of the epigenome. This mini-review is a summary of the current state of knowledge about the processes of epigenetic control of gene expression involved in the pathogenesis of endometriosis.

scholarly journals Cellular and molecular partners involved in gut morphogenesis and differentiation

1998 ◽  
Vol 353 (1370) ◽  
pp. 847-856 ◽  
Author(s):  
M. Kedinger ◽  
O. Lefebvre ◽  
I. Duluc ◽  
J. N. Freund ◽  
P. Simon–Assmann
Keyword(s):  
Cross Talk ◽  
Mesenchymal Cell ◽  
Cell Compartment ◽  
Paracrine Factors ◽  
Cell Matrix ◽  
Epithelial Cell Migration ◽  
Extracellular Matrix Molecules ◽  
Proliferation And Differentiation ◽  
Cell Matrix Adhesion

The intestinal mucosa represents an interesting model to study the cellular and molecular basis of epithelial–mesenchymal cross–talk participating in the development and maintenance of the digestive function. This cross–talk involves extracellular matrix molecules, cell–cell and cell–matrix adhesion molecules as well as paracrine factors and their receptors. The cellular and molecular unit is additionally regulated by hormonal, immune and neural inputs. Such integrated cell interactions are involved in pattern formation, in proximodistal regionalization, in maintenance of a gradient of epithelial proliferation and differentiation, and in epithelial cell migration. We focus predominantly on two aspects of these integrated interactions in this paper: (i) the role of basement membrane molecules, namely laminins, in the developmental and spatial epithelial behaviour; and (ii) the importance of the mesenchymal cell compartment in these processes.

Role of CPI-17 in the regulation of endothelial cytoskeleton

2004 ◽  
Vol 287 (5) ◽  
pp. L970-L980 ◽  
Author(s):  
Irina A. Kolosova ◽  
Shwu-Fan Ma ◽  
Djanybek M. Adyshev ◽  
Peyi Wang ◽  
Motoi Ohba ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Molecular Mechanisms ◽  
Rho Kinase ◽  
Focal Adhesions ◽  
Endothelial Permeability ◽  
Dominant Negative ◽  
Microvascular Endothelial Cell ◽  
Microvascular Endothelial ◽  
Lung Microvascular Endothelial Cell

We have previously shown that myosin light chain (MLC) phosphatase (MLCP) is critically involved in the regulation of agonist-mediated endothelial permeability and cytoskeletal organization (Verin AD, Patterson CE, Day MA, and Garcia JG. Am J Physiol Lung Cell Mol Physiol 269: L99–L108, 1995). The molecular mechanisms of endothelial MLCP regulation, however, are not completely understood. In this study we found that, similar to smooth muscle, lung microvascular endothelial cells expressed specific endogenous inhibitor of MLCP, CPI-17. To elucidate the role of CPI-17 in the regulation of endothelial cytoskeleton, full-length CPI-17 plasmid was transiently transfected into pulmonary artery endothelial cells, where the background of endogenous protein is low. CPI-17 had no effect on cytoskeleton under nonstimulating conditions. However, stimulation of transfected cells with direct PKC activator PMA caused a dramatic increase in F-actin stress fibers, focal adhesions, and MLC phosphorylation compared with untransfected cells. Inflammatory agonist histamine and, to a much lesser extent, thrombin were capable of activating CPI-17. Histamine caused stronger CPI-17 phosphorylation than thrombin. Inhibitory analysis revealed that PKC more significantly contributes to agonist-induced CPI-17 phosphorylation than Rho-kinase. Dominant-negative PKC-α abolished the effect of CPI-17 on actin cytoskeleton, suggesting that the PKC-α isoform is most likely responsible for CPI-17 activation in the endothelium. Depletion of endogenous CPI-17 in lung microvascular endothelial cell significantly attenuated histamine-induced increase in endothelial permeability. Together these data suggest the potential importance of PKC/CPI-17-mediated pathway in histamine-triggered cytoskeletal rearrangements leading to lung microvascular barrier compromise.

Sign in / Sign up

Export Citation Format

Share Document