Tissue factor (TF) is a cell-associated receptor for coagulation factor VIIa (FVIIa) that initiates the coagulation cascade and transmits intracellular signals through protease activated receptors (PARs). This thesis documents for the first time that in human glioma cells (U373) oncogenic epidermal growth factor receptor (EGFRvIII) simultaneously upregulates the expression of several elements of the TF pathway (TF, FVIIa, PAR-1 and PAR-2). In the absence of EGFRvIII, TF triggers tumor formation, albeit with a long latency, while treatment of glioma cells with FVIIa activates MAPK phosphorylation and stimulates the expression of angiogenic factors (VEGF and IL-8). Moreover, selective targeting of the host (mouse) TF reveals its independent role in glioma tumorigenesis. We propose that TF may represent an attractive potential target to treat human brain tumors.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.116094 |
| Date | January 2008 |
| Creators | Magnus, Nathalie. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 003132361, proquestno: AAIMR67036, Theses scanned by UMI/ProQuest. |
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