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Research ArticleExperimental Studies
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Transcriptional Induction of SERPINE1 and Fibrinolysis Inhibition as Predominant Effects of Glucocorticoids on the Cancer Coagulome

FLORIANE RACINE, CHRISTOPHE LOUANDRE, JULIEN DEMAGNY, CORINNE GODIN, ZUZANA SAIDAK and ANTOINE GALMICHE
Anticancer Research August 2024, 44 (8) 3269-3276; DOI: https://doi.org/10.21873/anticanres.17145
FLORIANE RACINE
1UR7516, CHIMERE, Université de Picardie Jules Verne, Amiens, France;
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CHRISTOPHE LOUANDRE
2Service de Biochimie, Centre de Biologie Humaine, CHU Amiens, Amiens, France;
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JULIEN DEMAGNY
3Service d’Hématologie, Centre de Biologie Humaine, CHU Amiens, Amiens, France
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CORINNE GODIN
1UR7516, CHIMERE, Université de Picardie Jules Verne, Amiens, France;
2Service de Biochimie, Centre de Biologie Humaine, CHU Amiens, Amiens, France;
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ZUZANA SAIDAK
1UR7516, CHIMERE, Université de Picardie Jules Verne, Amiens, France;
2Service de Biochimie, Centre de Biologie Humaine, CHU Amiens, Amiens, France;
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ANTOINE GALMICHE
1UR7516, CHIMERE, Université de Picardie Jules Verne, Amiens, France;
2Service de Biochimie, Centre de Biologie Humaine, CHU Amiens, Amiens, France;
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  • For correspondence: galmiche.antoine{at}chu-amiens.fr
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    Figure 1.

    Glucocorticoid regulation of coagulome-related genes in human tumors. (A) Pearson correlation between the GR-activity score for 54 solid cancer cell lines from the NCI-60 and their expression of the 85 coagulation-related genes from KEGG. (B) RNAseq data from the Gene Expression Omnibus (GSE159546) were used to evaluate the changes in expression of coagulation-related genes from KEGG (n=85). The log2 change in expression was calculated for five NSCLC cell lines treated with hydrocortisone (2.75 μM, 8 h). The top 21 genes either up-regulated or down-regulated are shown. (C, D) Pan-cancer correlation analysis of the GR-activity score and SERPINE1 expression, using gene expression data from 19 common human cancers from TCGA (C) and PAAD-TCGA (D).

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    Figure 2.

    The specificity of coagulome regulation by glucocorticoids in oral squamous cell carcinoma. QPCR analysis of the expression of F3, PLAU and SERPINE1 in PE/CA-PJ41. Cells were treated with dexamethasone (10 μM), aldosterone (1 μM), GW4064 (1 μM), Vitamin D3 (100 nM), bexarotene (10 μM) and T3 hormone (1 μM), with or without TNFα (25 ng/ml) for 24 h. *indicates p<0.05 compared to control conditions with Student’s t test.

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    Figure 3.

    Functional consequences of glucocorticoid treatment of oral squamous cell carcinoma cells on thrombin and plasmin activation. (A, B) Functional assays using thrombin (A) and uPA (B) substrates and culture supernatants of PE/CA-PJ41 cells exposed to dexamethasone (1 μM) +/− TNFα (25 ng/ml) for six days. The enzymatic activity is expressed as arbitrary units. The left panel is a representative experiment. The right panel is a quantification based on three independent experiments. (C) D-dimer levels in PE/CA-PJ41 supernatants exposed to dexamethasone (1 μM) +/− TNFα (25 ng/ml) for three days. Coagulation was triggered with 10% plasma 24 h before D-dimer measurements. *p<0.05 compared to control condition with Student’s t-test.

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Anticancer Research: 44 (8)
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Transcriptional Induction of SERPINE1 and Fibrinolysis Inhibition as Predominant Effects of Glucocorticoids on the Cancer Coagulome
FLORIANE RACINE, CHRISTOPHE LOUANDRE, JULIEN DEMAGNY, CORINNE GODIN, ZUZANA SAIDAK, ANTOINE GALMICHE
Anticancer Research Aug 2024, 44 (8) 3269-3276; DOI: 10.21873/anticanres.17145

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Transcriptional Induction of SERPINE1 and Fibrinolysis Inhibition as Predominant Effects of Glucocorticoids on the Cancer Coagulome
FLORIANE RACINE, CHRISTOPHE LOUANDRE, JULIEN DEMAGNY, CORINNE GODIN, ZUZANA SAIDAK, ANTOINE GALMICHE
Anticancer Research Aug 2024, 44 (8) 3269-3276; DOI: 10.21873/anticanres.17145
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Keywords

  • Cancer-associated thrombosis
  • coagulome
  • glucocorticoids
  • SERPINE1/Plasminogen Activator Inhibitor-1
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