Lost in disruption: Role of proteases in glioma invasion and progression

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• 作者：Rolf Mentlein^a ; ^{rment@anat.uni-kiel.de} ; Kirsten Hattermann^a ; Janka Held-Feindt^b
• 关键词：ADAM ; a disintegrin and metalloproteinase ; ADAMTS ; ADAMs with thrombospondin motifs ; bFGF ; basic fibroblast growth factor ; ECM ; extracellular matrix ; EGF ; epidermal growth factor ; FAP ; fibroblast activation protein ; GAG ; glycosaminoglycan ; GFAP ; glial fib
• 刊名：Biochimica et Biophysica Acta (BBA)/Reviews on Cancer
• 出版年：2012
• 期刊代码：23_0304419x
• 类别：bio
• 出版时间：April, 2012
• 卷：1825
• 期：2
• 页码：178-185
• 文件大小：732 K

摘要

A characteristic feature of malignant glial tumors (gliomas) is their tendency to diffusely infiltrate the nervous system preventing their complete surgical resection. Proteases play a decisive role in this malignant process, either by degradation of brain extracellular matrix (ECM) components, adhesion molecules, or by regulating the activity of growth and chemotactic factors. Secreted matrix metalloproteinases (MMPs) and ADAMTS proteases (ADAMs with thrombospondin motifs) cleave different ECM components like the proteoglycans (lecticans) aggrecan, versican, neurocan and brevican with selective preferences; they are further regulated by endogenous inhibitors and activating metallo- and serine proteases. Cell surface proteases of the ADAM family (A Disintegrin And Metalloproteinase), but also serine proteases regulate the activity of growth factors and chemokines that act as autocrine / paracrine stimulators within gliomas. Thus, proteases play a decisive role for the spread and growth of gliomas and are prominent targets for their therapy.