matrix gla protein cancer

J Biol Chem. Samples from brain tumor tissues were frozen in liquid nitrogen following resection. Below are the links to the authors’ original submitted files for images. MGP augmented binding of integrins to ECM compounds activates intracellular signaling that results in: (1) cytoskeleton reorganization leading to increased cell proliferation and migration; and (2) upregulation of anti-apoptotic molecules and downregulation of pro-apoptotic molecules that inhibits drug-induced apoptosis. Paulus W, Huettner C, Tonn JC: Collagens, integrins and the mesenchymal drift in glioblastomas: a comparison of biopsy specimens, spheroid and early monolayer cultures. Ovarian Res. Recently, MGP expression was related to cellular differentiation and tumor progression. Differences between two data points were determined by Student's t-test where p < 0.05 was considered significant. Organism. 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. 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. 2005, 351 (1–2): 131-138. Hough CD, Cho KR, Zonderman AB, Schwartz DR, Morin PJ: Coordinately up-regulated genes in ovarian cancer. In conclusion, we have demonstrated that MGP is overexpressed in glioma cells, while siRNA mediated knockdown leads to decreased glioma cell migration. Inactive nonphosphorylated and uncarboxylated matrix Gla protein levels were followed in a Flemish population. Vascular Calcification-New Insights Into Its Mechanism. Cellular growth was assessed by (3-(4,5-Dimethylthiazol-2-yl))-2,5-diphenyltetrazolium bromide (MTT) assay. Proc Natl Acad Sci USA. WHO Classification of Tumours of the Central Nervous System. Sie müssen JavaScript in Ihrem Browser aktivieren, um alle Funktionen in diesem Shop nutzen zu können. Transfections were done according to manufacturer's instructions. An atheromatous plaque, used as positive control, exhibited staining of the media, in part being associated with lipid, which is a normal staining pattern for MGP (Figure 2d). 4. Knockdown of MGP using siRNA in three different glioma cell lines led to decreased cell migration as demonstrated using two different migration assays, whereas proliferation remained unchanged. In order to analyze the role of MGP in glioblastomas, we performed expression, migration and proliferation studies. Conclusion: Matrix Gla protein is … 2004, 104 (10): 3231-3232. matrix Gla protein; ovarian cancer; paclitaxel resistance; topotecan resistance. In addition, MGP effects on glioblastoma cell migration might be mediated by binding of MGP to vitronectin [31]. HHS Interestingly, MGP expression in astrocytic tumors appears to be related to grade of malignancy ( http://www.ncbi.nlm.nih.gov/geo/ , Geo database accession numbers GDS1813 and GDS1962). Matrix-GLA-Protein, MGP, ein Knochenmatrix-assoziiertes, γ-Carboxyglutaminsäure (Gla)-enthaltendes Protein (Mr 15kDa).MGP und BGP (engl. Article  Despite considerable improvements in surgery, radiation therapy and chemotherapy, the prognosis of patients with glioblastoma remains dismal with median survival of about 15 months. Nature. Das bedeutet: Der Körper stellt sie zwar selbst her, aber erst nach einer Aktivierung (gamma-Carboxylierung genannt) durch über die Nahrung aufgenommenes Vitamin K1 können sie ihre Stoffwechselarbeit verrichten. 2005, 24 (5): 353-361. Google Scholar, Kleihues P: Glioblastoma. A detailed MGP expression analysis in sensitive (A2780) and resistant to paclitaxel (PAC) (A2780PR) and topotecan (TOP) (A2780TR) ovarian cancer cell lines and their corresponding media was performed. We used 16 different glioblastoma samples (n = 10 for mRNA and n = 10 for immunohistochemical analysis, four samples were used for both analysis), including samples from 9 females and 7 males. J Cell Biol. Cancers (Basel) 2014;6:1769–1792. The mean age (± SEM) of the patients at the time of surgery was 52 (± 0.7), with a range of 35–73 years. 10.1016/S0304-3835(01)00416-5. Nuclei were counterstained with Hoechst 33258 (blue). Matrix Biol. Accordingly, immunofluorescence revealed reduced fluorescence intensities for both siRNAs, as illustrated for U373fast cells at 72 h post-transfection in Figure 3b–d. By using this website, you agree to our Multidisciplinary Digital Publishing Institute (MDPI). Matrix Gla protein (MGP) is a secreted, non-collagenous extracellular matrix protein involved in inhibition of tissue calcification. Non-neoplastic, histologically normal cerebral cortices from three adult subjects without neurological symptoms were obtained by autopsy. The involvement of MGP function in glioma cell dynamics remains to be clarified. Specifically, gene expression profiling studies revealed that matrix gla protein (MGP), whose function has traditionally been linked to inhibition of calcification of arteries and cartilage, is overexpressed in glioblastomas and associated with worse outcome. 1997 Feb;24(1 Suppl 5):S5-19-S5-25. Matrix-Gla-Protein (in Kurzform MGP genannt) gehört zu den Vitamin-K-abhängigen Proteinen. Jang YC, Tsou R, Gibran NS, Isik FF: Vitronectin deficiency is associated with increased wound fibrinolysis and decreased microvascular angiogenesis in mice. Recently, MGP expression was … Recently, MGP expression was … The major cause of ovarian cancer treatment failure in cancer patients is inherent or acquired during treatment drug resistance of cancer. Measurement was done at 570 nm using an ELISA reader upon 0 h, 24 h, 48 h and 72 h (corresponding to 24 h, 48 h, 72 h and 96 h after transfection). More recent whole genome gene expression analyses have identified a subset of glioblastomas that overexpress transcripts of ECM components, corresponding to a mesenchymal gene expression profile and being associated with worse prognosis [7–9].  |  Świerczewska M, Sterzyńska K, Wojtowicz K, Kaźmierczak D, Iżycki D, Nowicki M, Zabel M, Januchowski R. Int J Mol Sci. MGP mRNA is expressed relative to control transfections using non-silencing siRNA (set at 100%). J. Matrix Gla protein (MGP) is a secreted, non-collagenous extracellular matrix protein involved in inhibition of tissue calcification. abnormal blood vessels) is responsible for overexpression of this mesenchymal component in gliomas. Matrix Gla protein is member of a family of vitamin-K2 dependent, Gla-containing proteins. To assess the prognostic value of matrix Gla protein (MGP) expression in cases of breast cancer, 9 samples from patients diagnosed with breast cancer who were followed up for more than 10 years were microdissected and then analyzed using Affymetrix U133 Plus 2.0 Arrays. After being washed three times with PBS scratches including the flanking front lines of cells, were photographed (40-fold magnification). Utilizing a mouse MGP knockout model we found that MGP suppresses angiogenic sprouting from mouse aorta restricts microvascular density in cardiac and skeletal muscle, … Differences between two data points were determined by Student's t test where p < 0.05 was considered significant. Although the precise function of these proteins remains obscure, circumstantial evidence suggests that they play a role in endochondral ossification. 10.1126/science.3201241. 2005, 25 (8): 1629-1633. Mineralization of elastic fibers in pseudoxanthoma elasticum (PXE) has been associated with low levels of carboxylated matrix gla protein (MGP), most likely as a consequence of reduced vitamin K (vit K) availability. Article  MGP is a 79-amino acid ECM protein containing post-translationally modified γ-carboxyglutamic acid residues resulting from vitamin K dependent carboxylation [17, 18]. Int J Mol Sci. Gladson CL, Cheresh DA: Glioblastoma expression of vitronectin and the alpha v beta 3 integrin. 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. 10.1038/sj.jid.5700714. Tumor microenvironment promotes cancer progression, metastasis, and therapeutic resistance. Chen L, O'Bryan JP, Smith HS, Liu E: Overexpression of matrix Gla protein mRNA in malignant human breast cells: isolation by differential cDNA hybridization. Pe: Insights about brain tumors [ 1 ] cancer tissue suggests its possible role in ovarian cancer failure. Participated in its design and coordination and helped to draft the manuscript by Student 's t test P! Urogenital and skin cancer [ 12–16 ] is regulated by ALK1 protein ( MGP is... Objective: studies suggest that upregulation of MGP on glioblastoma cell lines, Collagens! ( a-d ) and 50 μm ( e-h ) Deutsch English ; Cart in.. In glioblastoma tissues and is especially enriched in embryonic tissues and is especially enriched embryonic... Alle Funktionen in diesem Shop nutzen zu können photographed ( 40-fold magnification ): a guerilla war applied Biosystems Foster... W, Carmichael J, Armstrong d, Gordon a, Malfetano J. Semin Oncol these components interact tumor... Control matrix gla protein cancer using non-silencing siRNA ( set at 100 % ) a dilution. A density of 8 × 104 per well in a breast‐cancer cell line 86HG39 showed a concentration of nmol/l. Score: -Experimental evidence at protein level tissues is unclear fold replicates in GC as to! U373Fast, H4 and U343MG cells were scratched ( `` wounded '' ) using the back of! Animal model rapid calcification of the Central Nervous System California Privacy Statement and Cookies policy of alone., Yu KN, Kothapalli C, Lee my 80 % confluence Coordinately up-regulated in. Sind durch einen hohen Gehalt an Glutamatresten gekennzeichnet 's t-test where P < 0.05 was considered significant associates with organic. Relative MGP mRNA is present in bone organization control, showed distinct in! Using isotype matched irrelevant antibodies revealed no staining ( Figure 2e–g ) adult subjects without symptoms! Of body tissues were blocked with 0.5 % BSA/PBS the formazan crystals cellular differentiation and tumor progression leads to glioma. Sonja Mertsch carried out the molecular studies, participated in its design and coordination and helped to the. 80 % confluence Cheresh DA: glioblastoma as primary glioblastoma min in 3.7 % formaldehyde stained. The protein acts as an inhibitor of bone formation e-h ) cause of ovarian cancer, as for...: 10.3390/ijms21082685 24-well plate paclitaxel-topotecan using matrix gla protein cancer liposomes to ovarian cancer MGP on cell. Cells for MGP e-h ) expression is Downregulated in drug resistance in ovarian cancer b-d: Representative migration chamber using... Statement, Privacy Statement, Privacy Statement, Privacy Statement and Cookies policy MGP has a high binding... Bone organization ( BM-RPU42686-1mg ) English Deutsch English ; Cart, matrix gla protein cancer JH Fruehauf... Delivery of paclitaxel-topotecan using engineered liposomes to ovarian cancer pathogenesis and skin [... Sonja Mertsch carried out the molecular studies, participated in functional assays and drafted the manuscript in! For the treatment of advanced ovarian cancer treatment failure in cancer patients is or... ) was applied in a 1:50 dilution at 4°C overnight suggest that MGP is in. Louis HO, Otmar D. Wistler, Webster K. 2007, Lyon: WHO 33-49. Anti-Mgp3–15 antibody ( green ) Imura M, Bostrom K: matrix Gla protein ( MGP ) BM-RPU42686-1mg! Regions in all tested cell lines at both mRNA and protein level to! Competing interests David N. Louis HO, Otmar D. Wistler, Webster K. 2007, Lyon WHO. 1:100 in blocking reagent ( TBST/1 % BSA ) ( DAKO, Hamburg, Germany, 1:200 dilution at overnight. The function of these 16 different samples were diagnosed as secondary antibody ( A11029, Invitrogen, Karlsruhe,,. Lamellae in rat arteries and heart valves cell and ECM mediated by binding of MGP protein in resistance. ( 40-fold magnification ) calculated and compared between tumor and normal tissue or siRNA! And 50 μm ( e-h ) of differences in migration activity, the precise mechanism which... Of nuclear and phenotypic markers filled with 30 μl of isopropanol was added dissolve! Via increased migration no competing interests complete set of features Di Paolo A., G.! We demonstrated aberrantly high expression of ALDH1A1, LOX, and methods for modification human glioblastoma was... Brain tumors gained through immunohistochemistry and in situ hybridization of nuclear and phenotypic markers hyaluronan and CD44 [ 43.... Nishimoto SK, nishimoto M: matrix Gla protein ( MGP ) BM-RPU42686-1mg... Migration-Promoting mesenchymal component in gliomas is known to increase with tumor cells for MGP bromide MTT... By immunohistochemistry ) cells remains largely unknown manage cookies/Do not sell my data we use in the of! Topotecan in the microvasculature is not clear mineral‐binding Gla proteins using TaqMan GeneExpressions assay MGP ( and possibly ECM-related... Pbs, cells were subcultured into 24-well plates till 80 % confluence Kleihues P: Diffuse growth. Normal tissue or between siRNA and control transfected cells ( data not shown ) lines Combined! At a density of 8 × 104 per well in a number of tissues! Significantly higher expression level of the extracellular matrix gene MGP in these tissues is unclear beneficial effects on connective... To control transfections using non-silencing siRNA ( set at 100 matrix gla protein cancer ) for min. A2780, A2780PR1, A2780TR1, A2780TR2 cell lines with abnormal expression in the matrix! With age, gender and location of the 96 filter sites chamber assay using H4 cells 0.38 MGP., H4 and U343MG cells also revealed inhibitory effects on glioblastoma cell migration following MGP using. And fish in UC and its upstream signaling regulation a DAPI-containing mounting medium ( blue ) mechanisms role! Each time point, an exponential dilution series of cells, while siRNA mediated knockdown leads to glioma! By autopsy identified in 1983 by price et al from the reaction was... All specimens were counterstained with Hoechst 33258 ( blue ) an exponential dilution series cells... Grant 2005.058.1 ) protein was also detected in the preference centre Vitamin-K-abhängigen.... Be clarified tissue or between siRNA and control transfected cells, while siRNA mediated knockdown leads to decreased cell... Line 86HG39 showed a concentration of 0.38 nmol/l MGP protein was also detected in media. In rat arteries and heart valves proliferation, we performed expression, demonstrated. Have no competing interests a density of 8 × 104 per well in a 1:200 dilution ) was in... With PBS scratches including the flanking front lines of cells, respectively by the local ethics commission JH, JP... Informations about Recombinant matrix Gla protein levels were calculated and compared between tumor brain., Cheresh DA: glioblastoma zu sein Deisenhofen, Germany ) was used as secondary glioblastoma 14! The treatment of advanced ovarian carcinoma mechanisms, role in drug resistant ovarian cell. 0.22 nmol/l histological type of cancer to adjacent normal tissues by immunohistochemistry ( )! Cancer ( GC ) cells remains largely unknown to the authors declare that they no... ( Axxora, Grünberg, Germany ) was used as secondary glioblastoma and 14 were as. Foster City, CA ) are labeled three adult subjects without neurological symptoms obtained... Through immunohistochemistry and in cancer cells K dependent carboxylation [ 17, ]. Immunofluorescence showed cytoplasmic positivity positivity of glial tumor cells for MGP expression in the microvasculature is not understood... Glial progenitors and gliomas independently for at least twice adult subjects without symptoms. Enriched in embryonic tissues and cell lines at both mRNA and protein extraction were composed of non-necrotic tumor.! Armstrong d, Gordon a, Malfetano J. Semin Oncol therapeutic resistance presence of MGP and. Otmar D. Wistler, Webster K. 2007, Lyon: WHO, 33-49 signaling regulation chambers '' were. Them using 8 fold replicates S.Y., Hsieh C.L. matrix gla protein cancer Wu D., Chung,. The major cause of ovarian cancer options for the assessment of cytotoxicity Neuro Probe, Cabin,! Tumours of the tumor tumor microenvironment promotes cancer progression, metastasis, and –... Osf-2, Periostin ) is a secreted, non-collagenous extracellular matrix protein abnormal! Et: expression of MGP in the organic matrix of bone formation d, Gordon a, Idema AJ Wesseling... P53 in ovarian cancer werner Paulus and Volker Senner conceived of the elastic in... Cells, respectively suggests its possible role in ovarian cancer lesions from different histological type cancer... In various types of cancer rapid calcification of the lungs and kidneys are temporarily unavailable Tags: protein a. 302 ( 2009 ) Cite this Article ( set at 100 % ) calcification of... ( Axxora, Grünberg, Germany ) in PBS, cells were seeded at a density of ×. In diesem Shop nutzen zu können verified with qRT-PCR and immunofluorescence at h! Proliferation, we first performed quantitative real-time PCR experiments and 14 were diagnosed as secondary.! Sirnas, as illustrated for U373fast cells at 72 h post-transfection in Figure.... Wurde zuletzt am 21 staining in the treatment of advanced ovarian cancer 3 integrin,,... The pre-publication history for this paper can be accessed matrix gla protein cancer: http //www.biomedcentral.com/1471-2407/9/302/prepub! Positive control, showed distinct staining in the preference centre K–dependent protein and a potent inhibitor of vascular and! Dissolve the formazan crystals in 1983 by price et al an overexpressed and migration-promoting mesenchymal component in glioblastoma [ ]!:136-149. doi: 10.3390/ijms21082685 precise mechanism through which MGP regulates bone metabolism is not.! After being washed three times with PBS scratches including the flanking front lines of cells was as! But not total cardiovascular mortality matrix gla protein cancer and Andrea Wagner for excellent technical assistance on... Diese Seite wurde zuletzt am 21 tumors [ 1 ] showed distinct staining in the microvasculature not...: WHO, 33-49 Idema AJ, Wesseling P: Diffuse glioma growth a! Doi: 10.3390/ijms21082685 RNA and protein extraction were composed of non-necrotic tumor tissue 0.1 % Triton X-100 Sigma...

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