scholarly journals Matrix Valency Regulates Integrin-mediated Lymphoid Adhesion via Syk Kinase

1999 ◽  
Vol 144 (4) ◽  
pp. 777-788 ◽  
Author(s):  
Dwayne G. Stupack ◽  
Erguang Li ◽  
Steve A. Silletti ◽  
Jacqueline A. Kehler ◽  
Robert L. Geahlen ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Lymphoid Cell ◽  
Lymphoid Cells ◽  
Cooperative Interaction ◽  
Antigen Receptors ◽  
Adhesion Proteins ◽  
Adhesion Sites ◽  
Syk Kinase ◽  
Ecm Proteins

Lymphocytes accumulate within the extracellular matrix (ECM) of tumor, wound, or inflammatory tissues. These tissues are largely comprised of polymerized adhesion proteins such as fibrin and fibronectin or their fragments. Nonactivated lymphoid cells attach preferentially to polymerized ECM proteins yet are unable to attach to monomeric forms or fragments of these proteins without previous activation. This adhesion event depends on the appropriate spacing of integrin adhesion sites. Adhesion of nonactivated lymphoid cells to polymeric ECM components results in activation of the antigen receptor-associated Syk kinase that accumulates in adhesion-promoting podosomes. In fact, activation of Syk by antigen or agonists, as well as expression of an activated Syk mutant in lymphoid cells, facilitates their adhesion to monomeric ECM proteins or their fragments. These results reveal a cooperative interaction between signals emanating from integrins and antigen receptors that can serve to regulate stable lymphoid cell adhesion and retention within a remodeling ECM.

Regulatory effects of stem cell factor and interleukin-4 on adhesion of human mast cells to extracellular matrix proteins

Blood ◽  
2002 ◽  
Vol 99 (3) ◽  
pp. 966-972 ◽  
Author(s):  
Axel Lorentz ◽  
Detlef Schuppan ◽  
Andreas Gebert ◽  
Michael P. Manns ◽  
Stephan C. Bischoff
Keyword(s):  
Extracellular Matrix ◽  
Mast Cell ◽  
Stem Cell ◽  
Cell Adhesion ◽  
Mast Cells ◽  
Stem Cell Factor ◽  
Collagen I ◽  
Interleukin 4 ◽  
Human Mast Cells ◽  
Ecm Proteins

Abstract Mast cells are inflammatory and immunoregulatory cells resident in tissues. They develop from bone marrow-derived progenitor cells that enter the tissue through the blood circulation. The specific localization and migration of mast cells in tissues is dependent on their interaction with extracellular matrix (ECM) proteins. Adhesion of human mast cells isolated from intestinal mucosa and cultured in the presence of stem cell factor (SCF) to ECM proteins is analyzed. It was observed that SCF is a unique cytokine enhancing mast cell adhesion to all tested ECM proteins (fibronectin, laminin, collagen I, III, IV, VI, XIV) up to 5-fold, particularly to fibronectin (54% ± 12% of mast cells) and to denatured collagens (40% ± 12% on cyanogen bromide-cleaved peptides of collagen I). Most noteworthy, preculture of mast cells with interleukin-4 (IL-4), in addition to SCF, reduced their potency to adhere to ECM proteins to one third compared to mast cells cultured with SCF alone. Mast cell adhesion was preferentially mediated by β1 integrins, and most cells expressed the ECM-binding integrins α2β1, α3β1, α4β1, α5β1, and αVβ3. SCF-induced mast cell adhesion was totally blocked by wortmannin and apigenin, indicating an involvement of phosphatidylinositol 3-kinase and mitogen-activated protein kinase, and it was related to an up-regulation of the HUTS-21 β1 epitope, which is associated with an activated conformation of β1. In conclusion, these data indicate that SCF induces the adhesion of cultured mast cells to ECM proteins, whereas IL-4 may promote detachment from the ECM.

Sperm protein 17 is expressed on normal and malignant lymphocytes and promotes heparan sulfate–mediated cell-cell adhesion

Blood ◽  
2001 ◽  
Vol 98 (7) ◽  
pp. 2160-2165 ◽  
Author(s):  
H. Marie Lacy ◽  
Ralph D. Sanderson
Keyword(s):  
Cell Adhesion ◽  
Heparan Sulfate ◽  
Lymphoid Cell ◽  
Specific Antigen ◽  
Cell Aggregation ◽  
Lymphoid Cells ◽  
Sperm Protein ◽  
And Migration ◽  
B Lymphoid ◽  
Sperm Protein 17

Sperm protein 17 (Sp17) is a highly conserved mammalian protein present on acrosome-reacted sperm that is thought to promote fertilization by binding sulfated carbohydrates of the oocyte zona pellucida. Although Sp17 was originally described as a testis-specific antigen, emerging evidence indicates that it may be more ubiquitously expressed than was previously thought. With the use of a specific antiserum, Sp17 was found to be present on the surface of malignant lymphoid cells, including B- and T-lymphoid cell lines, and on the surface of primary cells isolated from 2 patients having B-lymphoid tumors. Surprisingly, circulating B lymphocytes isolated from healthy volunteers also expressed Sp17, while circulating T lymphocytes exhibited only very weak expression. The role of Sp17 in promoting lymphoid cell adhesion was addressed with the use of recombinant Sp17 (rSp17). The rSp17 binds to the surface of myeloma cells but not to cells pretreated with heparitinase, an enzyme that removes heparan sulfate from the cell surface. Moreover, rSp17 promotes extensive aggregation of cells that express the syndecan-1 heparan sulfate proteoglycan, but in contrast, cells lacking syndecan-1 expression fail to aggregate in the presence of rSp17. These findings suggest that Sp17 promotes heparan sulfate–mediated cell aggregation and thereby plays a role in regulating adhesion and migration of normal and malignant lymphocytes.

scholarly journals Surface Modification of PDMS-Based Microfluidic Devices with Collagen Using Polydopamine as a Spacer to Enhance Primary Human Bronchial Epithelial Cell Adhesion

Micromachines ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 132
Author(s):  
Mohammadhossein Dabaghi ◽  
Shadi Shahriari ◽  
Neda Saraei ◽  
Kevin Da ◽  
Abiram Chandiramohan ◽  
...  
Keyword(s):  
Cell Culture ◽  
Extracellular Matrix ◽  
Surface Modification ◽  
Cell Adhesion ◽  
Cell Attachment ◽  
Microfluidic Devices ◽  
Bronchial Epithelial ◽  
Ecm Proteins ◽  
Coating Methods ◽  
Organ On A Chip

Polydimethylsiloxane (PDMS) is a silicone-based synthetic material used in various biomedical applications due to its properties, including transparency, flexibility, permeability to gases, and ease of use. Though PDMS facilitates and assists the fabrication of complicated geometries at micro- and nano-scales, it does not optimally interact with cells for adherence and proliferation. Various strategies have been proposed to render PDMS to enhance cell attachment. The majority of these surface modification techniques have been offered for a static cell culture system. However, dynamic cell culture systems such as organ-on-a-chip devices are demanding platforms that recapitulate a living tissue microenvironment’s complexity. In organ-on-a-chip platforms, PDMS surfaces are usually coated by extracellular matrix (ECM) proteins, which occur as a result of a physical and weak bonding between PDMS and ECM proteins, and this binding can be degraded when it is exposed to shear stresses. This work reports static and dynamic coating methods to covalently bind collagen within a PDMS-based microfluidic device using polydopamine (PDA). These coating methods were evaluated using water contact angle measurement and atomic force microscopy (AFM) to optimize coating conditions. The biocompatibility of collagen-coated PDMS devices was assessed by culturing primary human bronchial epithelial cells (HBECs) in microfluidic devices. It was shown that both PDA coating methods could be used to bind collagen, thereby improving cell adhesion (approximately three times higher) without showing any discernible difference in cell attachment between these two methods. These results suggested that such a surface modification can help coat extracellular matrix protein onto PDMS-based microfluidic devices.

scholarly journals Extracellular Matrix Proteins Confer Cell Adhesion-Mediated Drug Resistance Through Integrin αv in Glioblastoma Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Qi Yu ◽  
Weikun Xiao ◽  
Songping Sun ◽  
Alireza Sohrabi ◽  
Jesse Liang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Drug Resistance ◽  
Cell Adhesion ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Chemotherapeutic Agents ◽  
Luciferase Reporter ◽  
Akt Signaling Pathway ◽  
Ecm Proteins ◽  
Cells Cultured

Chemotherapy resistance to glioblastoma (GBM) remains an obstacle that is difficult to overcome, leading to poor prognosis of GBM patients. Many previous studies have focused on resistance mechanisms intrinsic to cancer cells; the microenvironment surrounding tumor cells has been found more recently to have significant impacts on the response to chemotherapeutic agents. Extracellular matrix (ECM) proteins may confer cell adhesion-mediated drug resistance (CAMDR). Here, expression of the ECM proteins laminin, vitronectin, and fibronectin was assessed in clinical GBM tumors using immunohistochemistry. Then, patient-derived GBM cells grown in monolayers on precoated laminin, vitronectin, or fibronectin substrates were treated with cilengitide, an integrin inhibitor, and/or carmustine, an alkylating chemotherapy. Cell adhesion and viability were quantified. Transcription factor (TF) activities were assessed over time using a bioluminescent assay in which GBM cells were transduced with lentiviruses containing consensus binding sites for specific TFs linked to expression a firefly luciferase reporter. Apoptosis, mediated by p53, was analyzed by Western blotting and immunocytofluorescence. Integrin αv activation of the FAK/paxillin/AKT signaling pathway and effects on expression of the proliferative marker Ki67 were investigated. To assess effects of integrin αv activation of AKT and ERK pathways, which are typically deregulated in GBM, and expression of epidermal growth factor receptor (EGFR), which is amplified and/or mutated in many GBM tumors, shRNA knockdown was used. Laminin, vitronectin, and fibronectin were abundant in clinical GBM tumors and promoted CAMDR in GBM cells cultured on precoated substrates. Cilengitide treatment induced cell detachment, which was most pronounced for cells cultured on vitronectin. Cilengitide treatment increased cytotoxicity of carmustine, reversing CAMDR. ECM adhesion increased activity of NFκB and decreased that of p53, leading to suppression of p53-mediated apoptosis and upregulation of multidrug resistance gene 1 (MDR1; also known as ABCB1 or P-glycoprotein). Expression of Ki67 was correlative with activation of the integrin αv-mediated FAK/paxillin/AKT signaling pathway. EGFR expression increased with integrin αv knockdown GBM cells and may represent a compensatory survival mechanism. These results indicate that ECM proteins confer CAMDR through integrin αv in GBM cells.

scholarly journals Extracellular Matrix Expression in Human Induced Pluripotent Stem Cell-Derived Optic Vesicles

2021 ◽  
pp. 1-10
Author(s):  
Heuy-Ching Wang ◽  
Ramesh R. Kaini ◽  
Christina L. Rettinger ◽  
Heuy-Ching Wang
Keyword(s):  
Extracellular Matrix ◽  
Stem Cell ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Pluripotent Stem Cell ◽  
Critical Role ◽  
Induced Pluripotent Stem Cell ◽  
Ecm Proteins ◽  
Optic Vesicles ◽  
Induced Pluripotent

Background: Human tissue/organ development is a complex, highly orchestrated process, regulated in part by the surrounding extracellular matrix (ECM). Every complex tissue, including the retina, has a unique ECM configuration that plays a critical role in cellular differentiation, adhesion, migration, and maturation. Aim: To characterize ECM expression of human induced pluripotent stem cell-derived optic vesicles (iPSC-OVs). Methods: A 3- dimensional (3D) in vitro suspension culture system was used to direct differentiation of human induced pluripotent stem cells (iPSCs) into optic vesicles (OVs). Stepwise differentiation of iPSCs into retinal progenitor cells was confirmed by sequential expression of OTX2, SOX1, SIX6, LHX2, PAX6, and CHX10. Expression of ECM genes in iPSC-derived OVs was analyzed by RT2 ProfilerTM PCR Array, whereas immunofluorescence staining was performed to detect ECM proteins in the OVs. Results: A number of cell adhesion molecules (CAMs) previously reported to be abundantly expressed in iPSCs such as E-cadherin, Intercellular adhesion molecule-1 (ICAM1), Integrin-α L, Integrin-α M, Integrin-α 6 were downregulated while neural and retina specific CAMs including neural cell adhesion molecule 1 (NCAM1), neural plakophilin-related armadillo repeat protein (NPRAP), Integrin-α 1 and Integrin-α 4 were upregulated. Several glycoproteins that have been reported to play key roles during retinogenesis, namely CD44, Tenascin C, Tenascin R, Neurocan, Neuroglycan C, Delta 2 Catenin, Vitronectin, and Reelin were also present. Conclusion: We have identified an array of ECM proteins that were expressed during retinogenesis. Further characterization of these proteins will lead to a better understanding of retinal development.

Anode Glow Discharge Plasma Treatment of Titanium Plates Facilitates Adsorption of Extracellular Matrix Proteins to the Plates

2005 ◽  
Vol 84 (7) ◽  
pp. 668-671 ◽  
Author(s):  
H. Yamamoto ◽  
Y. Shibata ◽  
T. Miyazaki
Keyword(s):  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Glow Discharge ◽  
Photoelectron Spectroscopy ◽  
Discharge Plasma ◽  
Matrix Proteins ◽  
Glow Discharge Plasma ◽  
Phosphate Adsorption ◽  
Ecm Proteins ◽  
Better Than

Glow discharge plasma (GDP) supplied to an anode (GDP+) promotes calcium phosphate adsorption onto titanium better than that supplied to a cathode (GDP-). However, the adsorption of extracellular matrix (ECM) proteins is crucial for cell adhesion to titanium. Since GDP+ induced both inorganic adsorption and cell adhesion, we hypothesized that the inorganic adsorption in a culture medium might affect the adsorption of the ECM proteins. In this study, ECM proteins adsorbed on titanium with and without GDP were examined by x-ray photoelectron spectroscopy. After 1 hr of incubation, increasing sodium adsorption on GDP+ specimens induced adsorption of ECM proteins as shown by NH+ and COO− signals without calcium adsorption. In contrast, since no specific adsorption of sodium on GDP-specimens was detected, GDP-did not contribute to the adsorption of ECM proteins. Thus, promotion of sodium adsorption of GDP+ was effective, at least in the initial ECM protein adsorption on a titanium surface.

scholarly journals An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

2012 ◽  
Vol 8 ◽  
pp. 787-803 ◽  
Author(s):  
Grazia Marano ◽  
Claas Gronewold ◽  
Martin Frank ◽  
Anette Merling ◽  
Christian Kliem ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Cell Adhesion ◽  
Binding Site ◽  
Tumor Cells ◽  
Biologically Active ◽  
Host Cells ◽  
Matrix Metalloproteinase 2 ◽  
Ecm Proteins

Oligosaccharides aberrantly expressed on tumor cells influence processes such as cell adhesion and modulation of the cell’s microenvironment resulting in an increased malignancy. Schmidt’s imidate strategy offers an effective method to synthesize libraries of various oligosaccharide mimetics. With the aim to perturb interactions of tumor cells with extracellular matrix proteins and host cells, molecules with 3,4-bis(hydroxymethyl)furan as core structure were synthesized and screened in biological assays for their abilities to interfere in cell adhesion and other steps of the metastatic cascade, such as tumor-induced angiogenesis. The most active compound, (4-{[(β-D-galactopyranosyl)oxy]methyl}furan-3-yl)methyl hydrogen sulfate (GSF), inhibited the activation of matrix-metalloproteinase-2 (MMP-2) as well as migration of the human melanoma cells of the lines WM-115 and WM-266-4 in a two-dimensional migration assay. GSF inhibited completely the adhesion of WM-115 cells to the extracellular matrix (ECM) proteins, fibrinogen and fibronectin. In an in vitro angiogenesis assay with human endothelial cells, GSF very effectively inhibited endothelial tubule formation and sprouting of blood vessels, as well as the adhesion of endothelial cells to ECM proteins. GSF was not cytotoxic at biologically active concentrations; neither were 3,4-bis{[(β-D-galactopyranosyl)oxy]methyl}furan (BGF) nor methyl β-D-galactopyranoside nor 3,4-bis(hydroxymethyl)furan, which were used as controls, eliciting comparable biological activity. In silico modeling experiments, in which binding of GSF to the extracellular domain of the integrin αvβ3 was determined, revealed specific docking of GSF to the same binding site as the natural peptidic ligands of this integrin. The sulfate in the molecule coordinated with one manganese ion in the binding site. These studies show that this chemically easily accessible molecule GSF, synthesized in three steps from 3,4-bis(hydroxymethyl)furan and benzoylated galactose imidate, is nontoxic and antagonizes cell physiological processes in vitro that are important for the dissemination and growth of tumor cells in vivo.

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