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.

Krenzlin H ，Lorenz V ，Alessandri B 《-》

Why are systemic glioblastoma metastases rare? Systemic and cerebral growth of mouse glioblastoma.

Mourad PD ，Farrell L ，Stamps LD ，Chicoine MR ，Silbergeld DL ... -  《surgical neurology》

The Importance of Thrombin in Cerebral Injury and Disease.

Krenzlin H ，Lorenz V ，Danckwardt S ，Kempski O ，Alessandri B ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Role of Thrombin in Central Nervous System Injury and Disease.

Shlobin NA ，Har-Even M ，Itsekson-Hayosh Z ，Harnof S ，Pick CG ... -  《Biomolecules》

Taking advantage of neural development to treat glioblastoma.

Glioblastoma (GBM) is by far the most common and most malignant primary adult brain tumor (World Health Organization grade IV), containing a fraction of stem-like cells that are highly tumorigenic and multipotent. Recent research has revealed that GBM stem-like cells play important roles in GBM pathogenesis. GBM is thought to arise from genetic anomalies in glial development. Over the past decade, a wide range of studies have shown that several signaling pathways involved in neural development, including basic helix-loop-helix, Wnt-β-catenin, bone morphogenetic proteins-Smads, epidermal growth factor-epidermal growth factor receptor, and Notch, play important roles in GBM pathogenesis. In this review, we highlight the significance of these pathways in the context of developing treatments for GBM. Extrapolating knowledge and concepts from neural development will have significant implications for designing better strategies with which to treat GBM.

Zhang Z ，Lin CC 《-》