Expression of the JAK and STAT superfamilies in human meningiomas

Object. The goal of this study was to investigate whether the janus kinase/ signal transducer and activator of transcription (JAK/STAT) signal transduc tion pathway is present and active in meningiomas. The results of these inv estigations are important for all meningioma therapies that, similar to int erferon-alpha-2B (IFN alpha-2B), depend on activation of this pathway for t heir effect. The authors were interested in evaluating the importance, if a ny, of the JAK/STAT path way in the biology and therapy for these tumors. Methods. Total proteins were extracted from 17 meningioma samples and the l evels of JAKs and STATs were determined by using Western blot analysis. Lev els of these proteins in meningiomas were compared with those found in norm al dura. The JAKs and STATs (with the exception of Jak3 and Tyk2) were pres ent both in the dura and in the meningiomas studied. In tumors JAK and STAT levels were always significantly higher than those found in normal dura. D ifferences in relative levels were found when meningiomas were subdivided a ccording to the current neuropathological criteria and the highest levels w ere found in transitional meningiomas. The authors also investigated, using tyrosine-phosphorylated Stat1 and Stat3 antibodies, whether STATs were act ivated in meningiomas and normal dura in vivo. Their results indicate that both Stat1 and Stat3 are phosphorylated in vivo in meningiomas and in the d ura: Furthermore, in vitro experiments in which two independent short-term cultures obtained from freshly dissected meningioma samples were used indic ated that Stat1 and Stat3 are phosphorylated in response to treatment with IFN alpha-2B. Exposure of meningioma cells to IFN alpha-2B leads to nuclear translocation of tyrosine-phosphorylated Stat1 and Stat3, as demonstrated by immunocytochemical analysis. Conclusions. The results of this study indicate that the JAK and STAT famil ies of proteins are important effecters in brain tumors and support the ide a that the effects of IFN alpha in vivo are direct and not mediated by the immune system. This suggests a role for modulation of STAT transcription fa ctors in inhibiting meningioma cell proliferation.