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Mechanisms of Glioma Invasion: Role of Matrix-Metalloproteinases

Published online by Cambridge University Press:  18 September 2015

J.H. Uhm ,
N.P. Dooley ,
J.-G. Villemure  and
V.W. Yong
J.H. Uhm
Affiliation:
Brain Tumour Research Group, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University, Montreal.
N.P. Dooley
Affiliation:
Brain Tumour Research Group, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University, Montreal.
J.-G. Villemure
Affiliation:
Brain Tumour Research Group, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University, Montreal.
V.W. Yong*
Affiliation:
Brain Tumour Research Group, Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University, Montreal.
*
Departments of Oncology and Cllinical Neurosciences, University of Calgary, 3330 Hospital Drive N.W., Calgary, Alberta, Canada T2N 4N1
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Abstract:

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One of the most lethal properties of high grade gliomas is their ability to invade the surrounding normal brain tissue, as infiltrated cells often escape surgical resection and inevitably lead to tumour recurrence. The consequent poor prognosis and survival rate underscore the need to further understand and target the cellular mechanisms that underly tumour invasiveness. Proteases which degrade the surrounding stromal cells and extracellular matrix proteins have been demonstrated to be critical effectors of invasion for tumours of both central and peripheral origin. Within the nervous system, the role of metalloproteinases as well as other classes of proteases in mediating the invasive phenotype of high grade gliomas has been an intense area of research. We present in this article a review of this literature and address the possibility that these proteases and the biochemical pathways that regulate their expression, such as protein kinase C, may represent potential targets in the therapy of high grade gliomas.

Résumé:

RÉSUMÉ:

Une des propriétés les plus léthales des gliomes à haut degré de malignité est leur capacité d'envahir le tissu cérébral normal avoisinant, cette infiltration maligne échappant souvent à la résection chirurgicale, ce qui conduit inévitablement à la récidive tumorale. Le pronostic sombre et le taux de survie faible dé démontrent la nécessité de mieux comprendre et de cibler les mécanismes cellulaires sous-jacents au caractère envahissant de ces tumeurs. Il a été démontré que les protéases qui dégradent les cellules du stroma avoisinant et les protéines de la matrice extracellulaire sont des effectrices critiques de l'invasion par les tumeurs d'origine centrale et périphérique. Le rôle des métalloprotéinases et des autres classes de protéases dans la médiation de l'invasion du système nerveaux par les gliomes très malins a fait l'objet de recherches intenses. Nous présentons une revue de cette littérature et nous considérons la possibilité que ces protéases et les voies biochimiques qui régulent leur expression, telles la protéine kinase C, pourraient être ciblées dans le traitment des gliomes de haut grade.

Type
Review Articles
Information
Canadian Journal of Neurological Sciences , Volume 24 , Issue 1 , February 1997 , pp. 3 - 15
Copyright
Copyright © Canadian Neurological Sciences Federation 1997

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