The K.G. McKenzie award lecture--1986. Effects of extracellular matrix proteins on the growth and differentiation of an anaplastic glioma cell line.

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 cytoplasmic 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.(ABSTRACT TRUNCATED AT 250 WORDS)