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Suppression of Glioma Growth in Vitro and in Vivo by Glia Maturation Factor¹

Department of Neurology, Division of Neurochemistry and Neurobiology, University of Iowa College of Medicine, and Veterans Administration Medical Center, Iowa City, Iowa 52242

Glia maturation factor (GMF), a 14,000 M_r acidic protein of the brain, is capable of promoting differentiation of cultured astroblasts. In this study we report the effect of GMF on two glioma cell lines: the C6 line, of rodent origin, and the HG-1 line, of human origin. When tested in culture, GMF promotes the initial growth of the two cell lines when the cells are sparse but limits proliferation by restoring contact inhibition when the cells are confluent. Cell cycle analysis confirms the arrest of the cells at the G₀/G₁ phase when the tumor cells are contact inhibited by GMF. When C6 cells are inoculated into the athymic (nude) mice at a s.c. site, a single solid tumor grows out with a 100% take. Intraperitoneal injection of GMF leads to the slowing down of tumor growth. That the in vivo effect of GMF is not due to cytotoxicity is evidenced by the lack of necrosis and by the appearance of more mature astrocytic cells in the tumors. The results lend support to the concept of GMF as a cellular regulator and suggest the therapeutic potential of GMF for brain tumors.

¹ This work was supported by the following grants to R.L.: VA Merit Review and Career Investigatorship Awards, National Science Foundation Grant BNS-8308341, National Cancer Institute Grant CA-31796, Diabetes-Endocrinology Research Center Grant AM-25295, and University of Iowa Cancer Center Grant.

² To whom requests for reprints should be addressed, at Department of Neurology, University of Iowa Hospital, Iowa City, IA 52242.

Received 3/17/86. Revised 6/23/86. Accepted 6/30/86.