Investigation of maturation provocative therapy in murine neuroblastomas was performed with dibutyryl cAMP, prostaglandin E_1 and papaverine or BL 191, but the results were not so satisfactory for the clinical application. It was lately found, however, that a protein factor obtained from the culture medium of glioblasts was rather promising effect for this kind of the therapy in Neuro2a, NS-20Y and NIE-115. This was different from the glial factor of Monard et al [Proc. Nat. Acad. Sci. 70: 1894, 1973] and was named glia-derived growth inhibitory factor (GDGIF), because of its inhibitory activity on cell division besides promoting morphological differentiation and inhibiting DNA synthesis in vitro. The factor, though only partially purified yet, had an apparent molecular weight of 100,000 and an isoelectric point of 5.0-7.5, and the activities were susceptible to protease digestion and inactivated by heat. The factor did not elevate the intracellular levels of cAMP and cGMP, and did not show any effect on glial cell lines, suggesting that its actions are highly specific to neuronal cells via cAMP-independent system. A significant prolongation of survival time was also noted in the neuroblastoma bearing A/J mice when the tumor cells were treated with the factor either before or after the inoculation.
