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Neoplasia (New York, N.Y.) 2002Integrin alpha(v)beta(3) is involved in varied cell biological activities, including angiogenesis, cell adhesion, and migration on several extracellular matrix... (Review)
Review
Integrin alpha(v)beta(3) is involved in varied cell biological activities, including angiogenesis, cell adhesion, and migration on several extracellular matrix components. Although alpha(v)beta(3) is not typically expressed in epithelial cells, it is expressed in macrophages, activated leukocytes, cytokine-stimulated endothelial cells, osteoclasts, and certain invasive tumors. Interestingly, the adhesion and migration of breast cancer cells on bone matrix are mediated, in part, by alpha(v)beta(3). Similar to breast cancer cells, prostate cancer cells preferentially metastasize to the bone. The biological events that mediate this metastatic pattern of prostate cancer are not well defined. This review discusses the role alpha(v)beta(3) plays in prostate cancer progression, with specific emphasis on bone metastasis and on alpha(v)beta(3) signaling in prostate cancer cells. The data suggest that alpha(v)beta(3), in part, facilitates prostate cancer metastasis to bone by mediating prostate cancer cell adhesion to and migration on osteopontin and vitronectin, which are common proteins in the bone microenvironment. These biological events require the activation of focal adhesion kinase and the subsequent activation of PI-3 kinase/Akt signaling pathway.
Topics: Cell Adhesion; Cell Movement; Disease Progression; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Humans; Macrophages; Male; Models, Biological; Neoplasm Metastasis; Neovascularization, Pathologic; Osteopontin; Phosphatidylinositol 3-Kinases; Phosphorylation; Prostatic Neoplasms; Protein-Tyrosine Kinases; Receptors, Vitronectin; Sialoglycoproteins; Vitronectin
PubMed: 11988838
DOI: 10.1038/sj.neo/7900224 -
Biomolecules Jan 2023Polyetheretherketone (PEEK) is a thermoplastic polymer that has been recently employed for bone tissue engineering as a result of its biocompatibility and mechanical...
Polyetheretherketone (PEEK) is a thermoplastic polymer that has been recently employed for bone tissue engineering as a result of its biocompatibility and mechanical properties being comparable to human bone. PEEK, however, is a bio-inert material and, when implanted, does not interact with the host tissues, resulting in poor integration. In this work, the surfaces of 3D-printed PEEK disks were functionalized with: (i) an adhesive peptide reproducing [351-359] h-Vitronectin sequence (HVP) and (ii) HVP retro-inverted dimer (D2HVP), that combines the bioactivity of the native sequence (HVP) with the stability toward proteolytic degradation. Both sequences were designed to be anchored to the polymer surface through specific covalent bonds via oxime chemistry. All functionalized PEEK samples were characterized by Water Contact Angle (WCA) measurements, Atomic Force Microscopy (AFM), and X-ray Photoelectron Spectroscopy (XPS) to confirm the peptide enrichment. The biological results showed that both peptides were able to increase cell proliferation at 3 and 21 days. D2HVP functionalized PEEK resulted in an enhanced proliferation across all time points investigated with higher calcium deposition and more elongated cell morphology.
Topics: Humans; Vitronectin; Polymers; Polyethylene Glycols; Ketones; Peptides; Surface Properties
PubMed: 36830615
DOI: 10.3390/biom13020246 -
Biochimica Et Biophysica Acta May 2003We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas...
We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters and in the subendothelial area of some blood vessels. In normal tissue, vitronectin had a homogeneous periductal occurrence, with local accumulation much lower than that in the carcinomas. Using a new solid phase radioligand assay, the vitronectin concentrations of extracts of carcinomas and normal breast tissue were determined and found to be indistinguishable. Comparison of the vitronectin and the hemoglobin concentrations of the extracts showed that their vitronectin content was not derived from blood contamination. Vitronectin mRNA was undetectable in both carcinomas and normal tissue. We conclude that vitronectin is not synthesised locally in breast tissue but derived by leakage from vessels, followed by extracellular accumulation in patterns distinctly different in carcinomas and normal tissue. The observation of a high vitronectin content in the carcinomas and its localisation in the tissue contributes to the clarification of the role of vitronectin in tumour biology in interaction with the plasminogen activation system and integrins.
Topics: Base Sequence; Breast; Breast Neoplasms; Carcinoma, Ductal, Breast; Case-Control Studies; Endothelium, Vascular; Extracellular Matrix; Female; Humans; Immunohistochemistry; Plasminogen Activator Inhibitor 1; RNA, Messenger; Radioligand Assay; Tumor Cells, Cultured; Vitronectin
PubMed: 12757937
DOI: 10.1016/s0925-4439(03)00059-0 -
Scientific Reports Mar 2021Borrelia miyamotoi, a member of the tick-borne relapsing fever spirochetes, shows a serum-resistant phenotype in vitro. This ability of B. miyamotoi may contribute to...
Borrelia miyamotoi, a member of the tick-borne relapsing fever spirochetes, shows a serum-resistant phenotype in vitro. This ability of B. miyamotoi may contribute to bacterial evasion of the host innate immune system. To investigate the molecular mechanism of serum-resistance, we constructed a membrane protein-encoding gene library of B. miyamotoi using Borrelia garinii strain HT59G, which shows a transformable and serum-susceptible phenotype. By screening the library, we found that bom1093 and bom1515 of B. miyamotoi provided a serum-resistant phenotype to the recipient B. garinii. These B. miyamotoi genes are predicted to encode P35-like antigen genes and are conserved among relapsing fever borreliae. Functional analysis revealed that BOM1093 bound to serum vitronectin and that the C-terminal region of BOM1093 was involved in the vitronectin-binding property. Importantly, the B. garinii transformant was not serum-resistant when the C terminus-truncated BOM1093 was expressed. We also observed that the depletion of vitronectin from human serum enhances the bactericidal activity of BOM1093 expressing B. garinii, and the survival rate of BOM1093 expressing B. garinii in vitronectin-depleted serum is enhanced by the addition of purified vitronectin. Our data suggests that B. miyamotoi utilize BOM1093-mediated binding to vitronectin as a mechanism of serum resistance.
Topics: Bacterial Proteins; Borrelia; Humans; Immunity, Innate; Relapsing Fever; Serum; Vitronectin
PubMed: 33750855
DOI: 10.1038/s41598-021-85069-w -
Frontiers in Bioscience (Landmark... Jan 2009The serine-protease urokinase (uPA) and its specific membrane receptor uPAR controls matrix degradation through the conversion of plasminogen into plasmin and play a... (Review)
Review
The serine-protease urokinase (uPA) and its specific membrane receptor uPAR controls matrix degradation through the conversion of plasminogen into plasmin and play a crucial role in a number of biological processes including local fibrinolysis, inflammation, angiogenesis, matrix remodelling during wound healing, tumor invasion and metastasis. Most of the cellular responses modulated by the uPA/uPAR system, including migration, cellular adhesion, differentiation, proliferation and apoptosis require transmembrane signaling, which is mediated by direct contacts of uPAR with a variety of extracellular proteins and membrane receptors, such as integrins, EGF receptor, high molecular weight kininogen, caveolin and the G-protein-coupled receptor FPRL1. As a result of these interactions, uPAR activates intracellular signalling molecules such as tyrosine- and serine-protein kinases, Src, focal adhesion kinase (FAK), Rac, extracellular-signal-regulated kinase (ERK)/mitogen- activated protein kinase (MAPK) and JAK/STAT, being part of a large "signalosome" interacting with several molecules on both the outside and inside of the cell. This review is focused on the biochemistry of the pathways affected by uPAR and its partners.
Topics: Calcium; Humans; MAP Kinase Signaling System; Neoplasms; Receptors, Urokinase Plasminogen Activator; Signal Transduction; Vitronectin; rho GTP-Binding Proteins
PubMed: 19273372
DOI: 10.2741/3550 -
Journal of Thrombosis and Haemostasis :... Dec 2006Allosteric disulfide bonds control protein function by mediating conformational change when they undergo reduction or oxidation. The known allosteric disulfide bonds are... (Review)
Review
Allosteric disulfide bonds control protein function by mediating conformational change when they undergo reduction or oxidation. The known allosteric disulfide bonds are characterized by a particular bond geometry, the -RHStaple. A number of thrombosis and thrombolysis proteins contain one or more disulfide bonds of this type. Tissue factor (TF) was the first hemostasis protein shown to be controlled by an allosteric disulfide bond, the Cys186-Cys209 bond in the membrane-proximal fibronectin type III domain. TF exists in three forms on the cell surface: a cryptic form that is inert, a coagulant form that rapidly binds factor VIIa to initiate coagulation, and a signaling form that binds FVIIa and cleaves protease-activated receptor 2, which functions in inflammation, tumor progression and angiogenesis. Reduction and oxidation of the Cys186-Cys209 disulfide bond is central to the transition between the three forms of TF. The redox state of the bond appears to be controlled by protein disulfide isomerase and NO. Plasmin(ogen), vitronectin, glycoprotein 1balpha, integrin beta(3) and thrombomodulin also contain -RHStaple disulfides, and there is circumstantial evidence that the function of these proteins may involve cleavage/formation of these disulfide bonds.
Topics: Allosteric Site; Animals; Blood Proteins; Disulfides; Enzyme Activation; Fibrinolysin; Fibrinolysis; Glycoproteins; Humans; Immunoglobulins; Integrin beta3; Oxidation-Reduction; Plasminogen; Protein Binding; Protein Conformation; Thrombomodulin; Thromboplastin; Thrombosis; Vitronectin
PubMed: 17002656
DOI: 10.1111/j.1538-7836.2006.02236.x -
BioMed Research International 2013After traumatic injuries to the nervous system, regrowing axons encounter a complex microenvironment where mechanisms that promote regeneration compete with inhibitory... (Review)
Review
After traumatic injuries to the nervous system, regrowing axons encounter a complex microenvironment where mechanisms that promote regeneration compete with inhibitory processes. Sprouting and axonal regrowth are key components of functional recovery but are often counteracted by inhibitory molecules. This review covers extracellular matrix molecules that support neuron axonal outgrowth.
Topics: Animals; Cells, Cultured; Disease Models, Animal; Extracellular Matrix Proteins; Fibronectins; Humans; Integrins; Laminin; Nerve Regeneration; Nerve Tissue Proteins; Neurons; Osteopontin; Peripheral Nerve Injuries; Spinal Cord Injuries; Thrombospondins; Vitronectin
PubMed: 24195084
DOI: 10.1155/2013/981695 -
Biophysical Journal Oct 2022The adaptability of proteins to their work environments is fundamental for cellular life. Here, we describe how the hemopexin-like domain of the multifunctional blood...
The adaptability of proteins to their work environments is fundamental for cellular life. Here, we describe how the hemopexin-like domain of the multifunctional blood glycoprotein vitronectin binds Ca to adapt to excursions of temperature and shear stress. Using X-ray crystallography, molecular dynamics simulations, NMR, and differential scanning fluorimetry, we describe how Ca and its flexible hydration shell enable the protein to perform conformational changes that relay beyond the calcium-binding site and alter the number of polar contacts to enhance conformational stability. By means of mutagenesis, we identify key residues that cooperate with Ca to promote protein stability, and we show that calcium association confers protection against shear stress, a property that is advantageous for proteins that circulate in the vasculature, like vitronectin.
Topics: Calcium; Vitronectin; Protein Binding; Hemopexin; Binding Sites; Crystallography, X-Ray; Protein Conformation
PubMed: 36056555
DOI: 10.1016/j.bpj.2022.08.044 -
International Journal of Molecular... Aug 2021Cell signaling mediated by the αv integrin plays a pivotal role in macrophage activation in various inflammatory processes, but its involvement in the pathogenesis of...
Cell signaling mediated by the αv integrin plays a pivotal role in macrophage activation in various inflammatory processes, but its involvement in the pathogenesis of dry eye disease (DED) remains unclear. In a murine model of DED, we found increased αv integrin expression in ocular surface macrophages. The αv integrins inhibitor c(RGDfK) ameliorated the corneal damage caused by DED, suggesting a pathogenic role for αv integrin. Because tear hyperosmolarity induces ocular inflammation in DED, a hyperosmolar culture of murine bone marrow-derived macrophages (BMDMs) is used to reproduce inflammation in vitro. However, the expression of proinflammatory cytokine mRNA was minimal, even though αv integrin was induced. In searching for components that are involved in αv integrin-mediated inflammation but that are missing from the culture model, we showed that the levels of vitronectin (VTN), a binding ligand of αv integrins, were increased in the tear fluid and conjunctival stroma of DED animals. The addition of VTN prominently enhanced hyperosmolarity-induced inflammation in BMDMs. Mechanistically, we showed that VTN/αv integrins mediated NF-κB activation to induce inflammatory gene expression in the BMDMs. Our findings indicate that interaction the of VTN with αv integrins is a crucial step in the inflammatory process in DED and suggests a novel therapeutic target.
Topics: Animals; Cell Line; Cytokines; Dry Eye Syndromes; Eye; Female; Gene Expression Regulation; Humans; Inflammation; Integrin alphaV; Macrophages; Mice; Mice, Inbred C57BL; Signal Transduction; THP-1 Cells; Tears; Vitronectin
PubMed: 34445121
DOI: 10.3390/ijms22168410 -
Molecules (Basel, Switzerland) Feb 2021Acute coronary syndrome (ACS) is a condition in which the coronary artery supplying blood to the heart is infarcted via formation of a plaque and thrombus, resulting in...
Acute coronary syndrome (ACS) is a condition in which the coronary artery supplying blood to the heart is infarcted via formation of a plaque and thrombus, resulting in abnormal blood supply and high mortality and morbidity. Therefore, the prompt and efficient diagnosis of ACS and the need for new ACS diagnostic biomarkers are important. In this study, we aimed to identify new ACS diagnostic biomarkers with high sensitivity and specificity using a proteomic approach. A discovery set with samples from 20 patients with ACS and 20 healthy controls was analyzed using mass spectrometry. Among the proteins identified, those showing a significant difference between each group were selected. Functional analysis of these proteins was conducted to confirm their association with functions in the diseased state. To determine ACS diagnostic biomarkers, standard peptides of the selected protein candidates from the discovery set were quantified, and these protein candidates were validated in a validation set consisting of the sera of 50 patients with ACS and 50 healthy controls. We showed that hemopexin, leucine-rich α-2-glycoprotein, and vitronectin levels were upregulated, whereas fibronectin level was downregulated, in patients with ACS. Thus, the use of these biomarkers may increase the accuracy of ACS diagnosis.
Topics: Acute Coronary Syndrome; Aged; Biomarkers; Female; Fibronectins; Glycoproteins; Hemopexin; Humans; Male; Mass Spectrometry; Middle Aged; Proteomics; Vitronectin
PubMed: 33672727
DOI: 10.3390/molecules26041136