Lost in disruption: role of proteases in glioma invasion and progression.
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.
Department of Anatomy, University of Kiel, 24098 Kiel, Germany. rment@anat.uni-kiel.de
Rolf
R
Mentlein
Kirsten
K
Hattermann
Janka
J
Held-Feindt
D000818:Animals; D001932:Brain Neoplasms / Q000201:enzymology* / Q000473:pathology*; D018450:Disease Progression; D005910:Glioma / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D009361:Neoplasm Invasiveness; D010447:Peptide Hydrolases / Q000378:metabolism*
D010447:Peptide Hydrolases