Prostaglandin E synthase is upregulated by Gas6 during cancer-induced venous thrombosis

Aghourian, Meghedi N., Lemarie, Catherine A., Bertin, Francois-Rene and Blostein, Mark D. (2016) Prostaglandin E synthase is upregulated by Gas6 during cancer-induced venous thrombosis. Blood, 127 6: 769-777. doi:10.1182/blood-2015-02-628867

Author Aghourian, Meghedi N.
Lemarie, Catherine A.
Bertin, Francois-Rene
Blostein, Mark D.
Title Prostaglandin E synthase is upregulated by Gas6 during cancer-induced venous thrombosis
Journal name Blood   Check publisher's open access policy
ISSN 1528-0020
Publication date 2016-02-11
Year available 2016
Sub-type Article (original research)
DOI 10.1182/blood-2015-02-628867
Open Access Status Not yet assessed
Volume 127
Issue 6
Start page 769
End page 777
Total pages 9
Place of publication Washington, DC, United States
Publisher American Society of Hematology
Language eng
Subject 2403 Immunology
1303 Specialist Studies in Education
2720 Hematology
1307 Cell Biology
Formatted abstract
Venous thromboembolism is a common complication of cancer. Based on recent evidence that (1) growth arrest-specific 6 (Gas6) regulates the expression of tissue factor during venous thrombosis, and (2) cancer promotes a procoagulant milieu, we hypothesize that Gas6 may be involved in cancer-induced coagulopathy. Venous thrombi were induced in both wild-type (WT) and Gas6-deficient (−/−) mice with cancer. WT mice with cancer developed larger thrombi than their healthy counterparts; these larger thrombi induced by cancer were not seen in Gas6−/− mice. Whole genome microarray analysis of differential gene expression in WT and Gas6−/− endothelial cells exposed to M27 murine lung carcinoma cells reveal that Gas6 increases prostaglandin E synthase (Ptges) expression in endothelial cells. This was confirmed using real-time polymerase chain reaction and immunofluorescence staining. Culture of WT endothelial cells with M27 increases the secretion of prostaglandin E2 (PGE2), the enzymatic product of Ptges, in WT but not in Gas6−/− endothelial cells. In WT endothelial cells, Ptges expression was regulated through extracellular signal-regulated kinase 1/2 phosphorylation (ERK1/2). In vitro, PGE2 activates platelets after binding to its receptor, EP3. In vivo, EP3 receptor antagonism reversed the effect of cancer-induced thrombosis in WT mice. These results show that Gas6, through upregulation of PGE2, contributes to cancer-induced venous thrombosis.
Keyword Hematology
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
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Created: Wed, 16 Nov 2016, 20:40:42 EST by Francois-rene Bertin on behalf of Learning and Research Services (UQ Library)