Production and Secretion of Adrenomedullin From Glial Cell Tumors and its Effects on cAMP Production

Abstract

Takahashi, K., F. Satoh, E. Hara, M. Sone, O. Murakami, T. Kayama, T. Yoshimoto and S. Shibahara. Production and secretion of adrenomedullin from glial cell tumors and its effects on cAMP production. Peptides 18(8)1117–1124, 1997.—The expression of adrenomedullin (ADM) and its mRNA was studied in human glial cell tumors and cultured glioblastoma cell lines, T98G and A172. Northern blot analysis showed that ADM mRNA was expressed in all brain tumors examined (three anaplastic astrocytomas and two glioblastomas multiforme) and in the glioblastoma cell lines. Immunoreactive (IR-) ADM was detectable in these brain tumors by radioimmunoassay (0.31–2.0 pmol/g wet weight), except for one anaplastic astrocytoma. Reverse phase high performance liquid chromatography of the tumor extracts showed a single peak eluting in the position of ADM-(1–52). IR-ADM concentrations in the cultured media of T98G cells were 205.5 ± 8.4 fmol/10 5 cells/24 h (mean ± SEM, n = 5). Treatment of T98G cells with interferon γ or interleukin 1β increased the expression levels of ADM mRNA and the IR-ADM concentrations in the cultured media, whereas tumor necrosis factor α decreased them in a dose-dependent manner. Treatment with synthetic ADM-(1–52) (10 −8 or 10 −7 mol/l) increased the cAMP concentrations in the cultured media of T98G cells. These findings suggest that ADM is secreted from glial cell tumors and is related to the pathophysiology of these tumors.