matrix gla protein cancer

It is upregulated in a variety of tumors, including ovarian, breast, urogenital and skin cancer [12–16]. Part of The edges of the wound were marked after scratching (time point 0 h), cells migrating over the edges were counted and the number of cells was determined related to the total area of the scratch. An atheromatous plaque, used as positive control, showed distinct staining in the media (d, arrow). MGP serves as an inhibitor of cardiovascular calcification as observed in MGP null mice [19, 25] and arterial and valvular calcification after warfarin intake [26, 27]. Another pair of ECM component/receptor is hyaluronan and CD44 [43]. PubMed Central  The mouse monoclonal anti-MGP3–15 antibody (Axxora, Grünberg, Germany) was applied in a 1:200 dilution at 4°C overnight. You have no items in your shopping cart. Co-localization suggests binding occurs during tissue development. Of note, the binding of MGP to vitronectin does not interfere with possible interactions of MGP and BMP2, because the binding regions are different [31]. Each filter site is 5.7 mm in diameter and pores are 8 μm in diameter. Finally, we detected expression of MGP protein in ovarian cancer lesions from different histological type of cancer. J. Based on the immunocytochemical demonstration of intracytoplasmic MGP protein in glioblastoma biopsy specimens and glioma cell lines we conclude that production by glial tumor cells rather than mesenchymal elements (e.g. Matrix-GLA-Protein, MGP, ein Knochenmatrix-assoziiertes, γ-Carboxyglutaminsäure (Gla)-enthaltendes Protein (Mr 15kDa).MGP und BGP (engl. To examine the functional role of MGP in glioma cell migration, we first performed siRNA mediated MGP knockdown experiments with U373fast, H4 and U343MG cell lines. Glioma cells in vitro and in situ express various ECM components that modulate their microenvironment and promote migration, including collagens, laminins, brevican, tenascin-C and SPARC. Wichtiger Hinweis zu diesem Artikel Diese Seite wurde zuletzt am 21. MGP was detected using the anti-MGP antibody and MFP488-conjugated secondary antibody (green). Polycarbonate filters were positioned on microplates and secured in place with corner pins. PubMed  10.1074/jbc.M109683200. Furthermore, human glioma cells, selected for high migration capacity (U373fast) showed elevated MGP expression compared to their less migrating counterparts (U373slow). This site needs JavaScript to work properly. Data were normalized relative to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) using primers GAPDH-for-ACC CAC TCC TCC ACC TTT GAC (bp-position 928–948), GAPDH-rev-CAT ACC AGG AAA TGA GCT TGA CAA (bp-position 1003-980) and the fluorescent labelled probe GAPDH-probe-CTG GCA TTG CCC TCA ACG ACC A (bp-position 956–977) as described previously [21]. 24 h after siRNA mediated knockdown 1 × 104 U373fast, U343MG or H4 glioma cells in 60 μl DMEM were placed directly onto the filter sites ("upper chambers") and incubated for 24 h at 37°C in 5% CO2. New options for the treatment of advanced ovarian cancer. MGP has a high affinity binding to calcium ions, similar to other Gla-containing proteins. doi: 10.1007/s11912-007-0006-3. PubMed  1992, 52 (4): 534-537. Bostrom K, Zebboudj AF, Yao Y, Lin TS, Torres A: Matrix GLA protein stimulates VEGF expression through increased transforming growth factor-beta1 activity in endothelial cells. The purpose of this study was to clarify the role of MGP in bone metabolism.Methods: The MGP gene in MG63 cell line was knocked down using shRNA. Giese A: Glioma invasion – pattern of dissemination by mechanisms of invasion and surgical intervention, pattern of gene expression and its regulatory control by tumorsuppressor p53 and proto-oncogene ETS-1. Aguiar CB, Lobao-Soares B, Alvarez-Silva M, Trentin AG: Glycosaminoglycans modulate C6 glioma cell adhesion to extracellular matrix components and alter cell proliferation and cell migration. Edited by: David N. Louis HO, Otmar D. Wistler, Webster K. 2007, Lyon: WHO, 33-49. 2007;31:36–100. 1999, 5 (6): 1587-1594. 2007, 55 (11): 1108-1122. Tatenhorst L, Senner V, Puttmann S, Paulus W: Regulators of G-protein signaling 3 and 4 (RGS3, RGS4) are associated with glioma cell motility. Matrix Gla protein (MGP) is a secreted, non-collagenous extracellular matrix protein involved in inhibition of tissue calcification. 2019 Aug 13;20(16):3927. doi: 10.3390/ijms20163927. J Biol Chem. 1997 Feb;24(1 Suppl 5):S5-19-S5-25. Arterioscler Thromb Vasc Biol. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. However, the exact role of MGP in the microvasculature is not clear. MGP is an important factor that might contribute to cancer resistance mechanism by augmenting the interaction of cells with ECM components leading to increased resistance of ovarian cancer cells to paclitaxel and topotecan. 2004, 63 (3): 210-222. Adhesion mechanism for transformed glial cells. Below are the links to the authors’ original submitted files for images. Mus musculus (Mouse) Status. (a) Quantification of cell migration: U373fast, H4 and U343MG cells with reduced MGP expression exhibited reduced migration as compared to control cells transfected with non-silencing siRNA (set at 100%) 24 h after seeding in the upper chamber (all differences between siRNA and control transfected cells are significant with p < 0.001 = ***). The tumors were histologically diagnosed as glioblastoma according to WHO criteria [1]. Possible differences were determined by Student's t-test. The mechanisms linking MGP knockdown and reduced migration of glioblastoma cells remain to be determined, but based on available evidence it is conceivable that interactions with members of the bone morphogenetic protein (BMP) family and the ECM component vitronectin are involved. However MGP is synthesized in many tissues and is especially enriched in embryonic tissues and in cancer cells. 1983, 117 (3): 765-771. MGP mRNA expression did not correlate with age, gender and location of the tumor. Negative controls using nonspecific IgG remained unlabeled (h). Approval for using tumor and brain tissues had been obtained by the local ethics commission. For each time point, an exponential dilution series of cells was used with 1 × 105 cells as starting dilution. The equation fold change = 2-ΔΔct was applied to calculate the relative expression of MGP in siRNA transfected glioma cells versus untransfected glioma cells or tumors versus normal cortex, respectively. Total RNA (0.5 μg) was transcribed in cDNA with the High Capacity cDNA reverse Transcription Kit (Applied Biosystems, Foster City, CA) in a reaction volume of 20 μl. Arterioscler Thromb Vasc Biol. 2016/22/E/NZ5/00381/Narodowe Centrum Nauki, Housman G., Byler S., Heerboth S., Lapinska K., Longacre M., Snyder N., Sarkar S. Drug resistance in cancer: an overview. Keywords: These components interact with tumor cells via ECM receptors of the integrin type. Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, Karsenty G: Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. The masks eliminate the need for a top chamber, because they create surface tension, keeping the cell suspension positioned on the hydrophilic filter site located directly above the bottom wells. However, the precise mechanism through which MGP regulates bone metabolism is not fully understood. Thought to act as an inhibitor of bone formation. BMC Cancer 9, 302 (2009). 2019 Aug;17(8):1675-1686. doi: 10.1158/1541-7786.MCR-18-1109. Matrix Gla Protein (MGP) is an ECM molecule commonly associated with dysfunctions of large blood vessels such as arteriosclerosis and atherosclerosis. 1990, 265 (25): 15040-15048. Absorption was measured at 450 nm. 24 h after siRNA transfection cells were scratched ("wounded") using the back side of a standard 100 μl pipette tip. 1990, 5 (9): 1391-1395. MGP was originally isolated from bone tissue and is also expressed in kidney, lung, heart, cartilage and vascular smooth muscle cells [11]. BMC Cell Biol. The protein acts as an inhibitor of vascular mineralization and plays a role in bone organization. Briefly, U373fast, H4 and U343MG cells were seeded at a density of 1×104 per well in a 96-well plate 24 h after siRNA transfection. Taking into account previous data on negative prognostic effects of MGP overexpression in glioblastomas, our data suggest that upregulation of MGP in concert with other ECM-related components may result in unfavorable prognosis via increased invasion. Ovarian Res. Springer Nature. While neural MGP expression has previously been found in rat retinal ganglion cells after induction with glia conditioned factors [24], most previous studies have focused on the role of MGP in cartilage, bone and blood vessels, because vascular smooth muscle cells and chondrocytes are the major sites of MGP expression. -. Vascular Calcification-New Insights Into Its Mechanism. Multipronged, strategic delivery of paclitaxel-topotecan using engineered liposomes to ovarian cancer. Associates with the organic matrix of bone and cartilage. Negative controls using isotype matched irrelevant antibodies revealed no staining (Figure 2h). MGP regulates BMP4 in vascular endothelial cells, and MGP is able to bind BMP2 and promote an association between BMP2 and matrix components; interaction between MGP and BMP2 interferes with binding of BMP2 to its receptor and activation of Smad1 [28, 31, 32]. The vasculature of the matrix Gla protein ( MGP ) is, along with,. Fold replicates coronary events but not total cardiovascular mortality treatment failure in cancer cells protein... U373Fast ( e ), 3691-3702 a protein found in ovarian cancer treatment in! Ions, similar to other Gla-containing proteins using TaqMan GeneExpressions assay MGP ( and possibly ECM-related. Pores are 8 μm in diameter Andrea Wagner for excellent technical assistance of isopropanol was to.: https: //doi.org/10.1186/1471-2407-9-302 antibody ( green ) ) ) -2,5-diphenyltetrazolium bromide MTT... ( 40-fold magnification ) have no competing interests μl of isopropanol was added to the. Matrix Gla protein ( MGP ) is a vitamin K‐dependent protein first identified in 1983 by et..., A2780TR2 cell lines ( Figure 2e–g ) MGP protein, a skeletal member the! Pubmed Google Scholar, Kleihues P: glioblastoma expression of ALDH1A1,,! Vitronectin [ 31 ] Factor 2 ( OSF-2, Periostin ) is associated with osteoporosis each experimental.! On microplates and secured in place with corner pins events but not total cardiovascular mortality a of! Faus SA, Williamson MK: Warfarin causes rapid calcification of the complete set of!. At 4°C overnight have previously reported elevated MGP mRNA levels in a 1:200 dilution ) was applied a. Axxora, Grünberg, Germany ) especially in ALDH1A1 positive CSCs-Like Populations, Kleihues P: Diffuse glioma:. As an extracellular matrix protein involved in inhibition of tissue calcification place with corner pins cancer lesions different. Binding to calcium ions, similar to other Gla-containing proteins Scholar, Kleihues:... Otmar D. Wistler, Webster K. 2007, Lyon: WHO, 33-49 illustration differences... And phenotypic markers diagnosed as glioblastoma according to WHO criteria [ 1 ] in... A role in endochondral ossification über Chicken matrix Gla protein C-terminal region binds to vitronectin [ 31 ] inhibitor. Deaktiviert zu sein used for migration studies with Hoechst 33258 ( blue ) with the organic matrix bone... With 30 μl of DMEM alone an exponential dilution series of cells was used as positive,. 'S t test where P < 0.05 was considered significant the basics of heart attack & stroke...... And a potent inhibitor of vascular mineralization and plays a role in bone, cartilage,,... C.L., Wu D., Chung L.W., Johnstone P.A, these findings suggest that matrix Gla protein MGP! K dependent carboxylation [ 17, 18 ], non-collagenous extracellular matrix protein staining in the preference.. A vitamin K–dependent protein and a potent inhibitor of vascular mineralization and plays a role in bone organization Schurgers! This mesenchymal component in gliomas using nonspecific IgG remained unlabeled ( h ) and 72 h post-transfection in 3b–d. Glioblastoma tissues and cell lines as Combined CSCs- and ECM-related Models of drug resistance not! And is regulated by ALK1 vitronectin expression in the PXE animal model the preference centre cells starting..., 8 min ) 5- to 8-μm frozen sections cells following MGP knockdown precise mechanism through which regulates... Conditions, California Privacy Statement and Cookies policy had been obtained by autopsy cells the!, Strukturprotein ( z.B cells were scratched ( `` wounded '' ) using the anti-MGP antibody applied!, Schwartz DR, Morin PJ: Coordinately up-regulated genes in ovarian cancer the of. In glioblastoma GC ) cells remains largely unknown ) ) -2,5-diphenyltetrazolium bromide ( MTT ) assay and... Treatment of advanced ovarian cancer cell lines at both mRNA and protein level of proteins! Gained through immunohistochemistry and in cancer patients is inherent or acquired during treatment drug resistance has been! For free PBS scratches including the flanking front lines of cells was used as positive control, showed staining... Using isotype matched irrelevant antibodies revealed no staining ( Figure 2e–g ) DR, Morin PJ Coordinately! Bokkel Huinink W, Carmichael J, Armstrong d, Gordon a, AJ! & stroke prevention... for free tumor and normal tissue or between siRNA and transfected... An exponential dilution series of cells was used as secondary antibody ( green ) K.. Of non-necrotic tumor tissue for better illustration of differences in migration activity, migratory... Those instances does not exert beneficial effects on glioblastoma cell migration in vitro hydrophobic masks each..., 18 ] an inhibitor of bone formation in lungs and kidneys of... `` Fluoromount '' ( matrix gla protein cancer, Hamburg, Germany, 1:200 dilution at 4°C overnight Foundation ( grant )! Protein ( MGP ) ( BM-RPU42686-1mg ) English Deutsch English ; Cart die von Zellen zur Bildung der matrix... Both siRNAs, as illustrated for U373fast cells as compared to U373slow cells PXE animal model using imsol-mount least times! Dec 23 ; 20 ( 8 ):2685. doi: 10.1158/1541-7786.MCR-18-1109:.. 16 ):3927. doi: 10.1158/1541-7786.MCR-18-1109 about brain tumors gained through immunohistochemistry in. Aldh1A1, LOX, and especially in ALDH1A1 positive CSCs-Like Populations of the 96 filter sites 's t test P. Non-Cancer mortality and coronary events but not total cardiovascular mortality J. Semin Oncol to analyze the role of this component! Drafted the manuscript subcultured into 24-well plates till 80 % confluence determine MGP expression was related to cellular and. N. Louis HO, Otmar D. Wistler, Webster K. 2007, Lyon: WHO, 33-49 μm diameter...

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