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Effects of Extracellular Matrix Proteins on the Growth and Differentiation of an Anaplastic Glioma Cell Line

Published online by Cambridge University Press:  18 September 2015

James T. Rutka*
Affiliation:
Department of Neurological Surgery, University of California, San Francisco
*
c/o The Editorial Office, Department of Neurological Surgery, 1360 Ninth Avenue, Suite 210, San Francisco, CA 94122 USA
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Abstract:

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Efforts to determine the factors responsible for reversing malignancy in the central nervous system may not only increase our understanding of the growth of primary human brain tumors, but may eventually prove to be of therapeutic benefit as well. We therefore devised a model system to study the effects of extracellular matrix (ECM) proteins on the malignant phenotype of an anaplastic glioma line, U-343 MG-A. Well-characterized cultures derived from normal human leptomeninges were grown to confluence and maintained for 2 weeks. The pia-arachnoid cells were then removed with detergent and base, leaving behind an ECM enriched in laminin, fibronectin, types I and IV collagen, and procollagen III. U-343 MG-A tumor cells planted on top of this normal ECM were profoundly growth inhibited, developed multiple slender cytoplastic processes similar to those of normal astrocytes, and expressed more GFAP per cell than did tumor cells growing on plastic alone. The growth of U-343 MG-A tumor cells in flasks coated with purified fibronectin or laminin was not significantly inhibited. However, U-343 MG-A cultures grown in flasks coated with type I or IV collagen showed decreased cellular proliferation and altered cell morphology. Conditioned medium from U-343 MG-A tumor cells growing on plastic alone contained a 64 kD activated metalloprotease. U-343 MG-A tumor cells growing on the pia-arachnoid ECM do not demonstrate such proteolytic activity. We conclude that the tumor cell microenvironment is extremely important in modulating the growth and differentiation of an anaplastic glioma cell line. It is hoped that an increased knowledge of the production of ECM components and their effects on malignant glioma cell growth, migration and differentiation will lead to the development of new approaches to improve the prospects of patients with primary malignant brain tumors.

Type
Special Features
Copyright
Copyright © Canadian Neurological Sciences Federation 1986

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