A5034090671- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Cell Adhesion Molecules Research
- Ovarian cancer diagnosis and treatment
- Cancer, Lipids, and Metabolism
- Blood Coagulation and Thrombosis Mechanisms
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Wnt/β-catenin signaling in development and cancer
- Immune cells in cancer
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
- Signaling Pathways in Disease
- Angiogenesis and VEGF in Cancer
- Cancer, Hypoxia, and Metabolism
- Tissue Engineering and Regenerative Medicine
- Cancer-related molecular mechanisms research
- Cancer-related gene regulation
- Cardiovascular Disease and Adiposity
- Cancer Immunotherapy and Biomarkers
- Galectins and Cancer Biology
- Cellular Mechanics and Interactions
- Sphingolipid Metabolism and Signaling
- MicroRNA in disease regulation
- Caveolin-1 and cellular processes
- Plasma Applications and Diagnostics
University of Notre Dame
2014-2024
Cancer Research Institute
2013-2024
Mike and Josie Harper Cancer Research Institute
2013-2024
Laboratoire de Biochimie
2017
Cancer Research Institute of the Slovak Academy of Sciences
2017
University of Missouri
2007-2016
Indiana University – Purdue University Indianapolis
2016
Indiana University School of Medicine
2016
Northwestern University
2003-2015
University of Missouri Hospital
2007-2012
Angiostatin, a proteolytic fragment of plasminogen, is potent antagonist angiogenesis and an inhibitor endothelial cell migration proliferation. To determine whether the mechanism by which angiostatin inhibits and/or proliferation involves binding to surface plasminogen receptors, we isolated proteins for from human umbilical vein cells. Binding studies demonstrated that bound in concentration-dependent, saturable manner. Plasminogen was unaffected 100-fold molar excess angiostatin,...
The laminin-5 component of the extracellular matrices certain cultured cells such as rat epithelial cell line 804G and human breast MCF-10A is capable nucleating assembly cell– matrix adhesive devices called hemidesmosomes when other are plated upon them. These also impede motility. In contrast, onto laminin-5–rich pp126 fail to assemble motile. To understand these contradictory phenomena, we have compared forms heterotrimeric secreted by with those cells, using a panel subunit-specific...
Angiostatin, a potent naturally occurring inhibitor of angiogenesis and growth tumor metastases, is generated by cancer-mediated proteolysis plasminogen. Human prostate carcinoma cells (PC-3) release enzymatic activity that converts plasminogen to angiostatin. We have now identified two components released PC-3 cells, urokinase (uPA) free sulfhydryl donors (FSDs), are sufficient for angiostatin generation. Furthermore, in defined cell-free system, activators [uPA, tissue-type activator...
By proteolytic modification of low abundant signaling proteins and membrane receptors, proteases exert potent posttranslational control over cell behavior at the postsecretion level. Hence, substrate discovery is indispensable for understanding biological role in vivo . Indeed, matrix metalloproteinases (MMPs), long associated with extracellular degradation, are increasingly recognized as important processing enzymes bioactive molecules. MS now primary proteomic technique detecting,...
Abstract Malignant ovarian ascites are rich in cellular components, membrane-bound vesicles, and soluble proteins. This study focused on the structure of vesicles their ability to promote invasion cultured malignant epithelium. Membrane were derived from women with stage I–IV nonmalignant gynecologic ascites. Isolated characterized by immunofluorescence Western blot analysis. Using gel zymography for matrix metalloproteinase (MMP) detection a colorimetric assay urokinase-type plasminogen...
Human lung mast cell tryptase is a trypsin-like serine proteinase that stored in granules and released by activated cells.Here we report potent activator of single-chain urinary-type plasminogen (scu-PA, or prourokinase), the zymogen form (u-PA).Activation was complete within 75 min using an enzyme:substrate molar ratio 1:50 accompanied cleavage scu-PA at Lys1S8-Ile1Se, generating active two-chain u-PA.The reaction dependent on enzyme concentration obeyed Michaelis-Menten kinetics.Kinetic...
Reversible modulation of cell-cell adhesion, cell-matrix and proteolytic activity plays a critical role in remodeling the neoplastic ovarian epithelium during metastasis, implicating cadherins, integrins, proteinases i.p. metastatic dissemination epithelial carcinoma (EOC). Aberrant differentiation is an early event carcinogenesis; thus, contrast to most carcinomas that lose E-cadherin expression with progression, abundant primary EOC. Metastasizing EOCs engage integrin-mediated adhesion...
Abstract Epidermal growth factor (EGF) receptor (EGFR) is frequently elevated in epithelial ovarian cancer, and E-cadherin expression often reduced advanced disease. In this study, we investigated a mechanism by which EGFR activation promotes disruption of adherens junctions through induction matrix metalloproteinase 9 (MMP-9). We show that down-modulates E-cadherin, broad spectrum MMP inhibition ameliorates EGF-stimulated junctional loss protein. MMP-9 involvement EGF-dependent...
Type I collagen stimulation of pro-matrix metalloproteinase (pro-MMP)-2 activation by ovarian cancer cells involves β1 integrin receptor clustering; however, the specific cellular and biochemical events that accompany MMP processing are not well characterized. Collagenolysis is required for pro-MMP-2 activation, denatured does elicit an MMP-2 response. Similarly, DOV13 bind to intact utilizing both α2β1 α3β1 integrins but interact poorly with collagenase-treated or thermally collagen....
A fluorogenic substrate for vertebrate collagenase and gelatinase, Dnp-Pro-Leu-Gly-Leu-Trp-Ala-D-Arg-NH2, was designed using structure-activity data obtained from studies with synthetic inhibitors other peptide substrates of collagenase. Tryptophan fluorescence efficiently quenched by the NH2-terminal dinitrophenyl group, presumably through resonance energy transfer. Increased accompanied hydrolysis or gelatinase purified culture medium porcine synovial membranes alkali-treated rabbit...
The epidermal growth factor receptor (EGFR) has been proposed as a key modulator of cadherin-containing intercellular junctions, particularly in tumors that overexpress this tyrosine kinase. Here the EGFR kinase inhibitor PKI166 and blocking antibody C225, both which are used clinically to treat head neck cancers, were determine effects inhibition on junction assembly adhesion oral squamous cell carcinoma cells. resulted transition from fibroblastic morphology more epithelial phenotype cells...