The involvement of thrombin in the pathogenesis of glioblastoma.
Prothrombin and its active derivative thrombin are key members of the coagulation system. The only site of extra-hepatic thrombin expression is the central nervous system (CNS), where it is involved in brain development, protection, and regeneration. Thrombin affects various degenerative and ischemic CNS diseases like Alzheimer's, multiple sclerosis, cerebral ischemia, and hemorrhage in a dose dependent manner. Additionally, the association of thrombin with various malignancies has recently become evident. Thrombin facilitates the interaction between tumor cells with platelets, endothelial cells, and the adhesion to matrix proteins in various tumor types. Consequently, thrombin enables tumor cell seeding and metastasis, resulting in increased tumor cell growth and angiogenesis. Despite the exceptional position of thrombin in the CNS, its involvement in brain tumor course and development has so far been largely neglected. Over the last decade, several studies found a detrimental effect of thrombin in the most devastating of all primary brain tumors, glioblastomas (GBM). This review highlights the current knowledge on the involvement of thrombin in the pathophysiology and clinical course of GBMs. © 2017 Wiley Periodicals, Inc.
Harvey Cushing Neuro-oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.|Institute for Neurosurgical Pathophysiology, University Medicine Mainz, Langenbeckstr.1, Mainz, 55101, Germany.
Harald
H
Krenzlin
Division of Newborn Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
Viola
V
Lorenz
Institute for Neurosurgical Pathophysiology, University Medicine Mainz, Langenbeckstr.1, Mainz, 55101, Germany.
Beat
B
Alessandri
D000818:Animals; D001932:Brain Neoplasms / Q000503:physiopathology*; D005909:Glioblastoma / Q000503:physiopathology*; D006801:Humans; D013917:Thrombin / Q000378:metabolism*
D013917:Thrombin
Glioblastoma; MAPK; MMP-9; PAR-1; PI3K; thrombin