The pro-migratory and pro-invasive role of the procoagulant tissue factor in malignant gliomas.
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 tumours. 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 point of view article 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.
Dützmann
Stephan
S
Experimental Neurosurgery, Goethe University Hospital Frankfurt, Germany.
Gessler
Florian
F
Harter
Patrick N
PN
Gerlach
Rüdiger
R
Mittelbronn
Michel
M
Seifert
Volker
V
Kögel
Donat
D
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D015687:Cell Hypoxia; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D005910:Glioma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D009336:Necrosis; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism; D010641:Phenotype; D044464:Receptor, PAR-2 / Q000378:metabolism; D015398:Signal Transduction; D013925:Thromboplastin / Q000378:metabolism*; D013927:Thrombosis / Q000473:pathology; D059016:Tumor Microenvironment
D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; D044464:Receptor, PAR-2; D013925:Thromboplastin