The pro-migratory and pro-invasive role of the procoagulant tissue factor in malignant gliomas

Stephan Dützmann, Florian Gessler, Patrick N. Harter, Rüdiger Gerlach, Michel Mittelbronn, Volker Seifert, Donat Kögel*

*Corresponding author for this work

Research output: Contribution to journalComment/debate

12 Citations (Scopus)

Abstract

During the infiltration process, glioma cells are known to migrate along preexisting anatomical structures such as blood vessels, axonal fiber tracts and the subependymal space, thereby widely invading surrounding CNS tissue. This phenomenon represents a major obstacle for the clinical treatment of these tumors. Several extracellular key factors and intracellular signaling pathways have been previously linked to the highly aggressive, invasive phenotype observed in malignant gliomas. The glioblastoma (GBM), which is the most malignant form of these tumors, is histologically characterized by areas of tumor necroses and pseudopalisading cells, the latter likely representing tumor cells actively migrating away from the hypoxic-ischemic core of the tumor. It is believed that intravascular thromboses play a major role in the emergence of hypoxia and intratumoral necroses in GBMs. One of the most highly upregulated prothrombotic factor in malignant gliomas is tissue factor (TF), a 47 kDa type I transmembrane protein belonging to the cytokine receptor superfamily. In a recent study, we provided evidence that TF/FVIIa signaling via the protease-activated receptor 2 (PAR-2) promotes cell growth, migration and invasion of glioma cells. In this Commentary & View, we outline the key molecular players involved in migration and invasion of gliomas, highlight the potential role of TF for the pro-migratory and pro-invasive phenotype of these tumors and discuss the underlying mechanisms on the cellular level and in the tumor microenvironment.

Original languageEnglish
Pages (from-to)515-522
Number of pages8
JournalCell Adhesion and Migration
Volume4
Issue number4
DOIs
Publication statusPublished - 2010
Externally publishedYes

Keywords

  • Blood coagulation
  • Brain tumor
  • Cancer stem cells
  • Hypoxia
  • MAP kinase
  • Tumor invasion

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