Expression of the JAK and STAT superfamilies in human meningiomas.
OBJECTIVE
The goal of this study was to investigate whether the janus kinase/signal transducer and activator of transcription (JAK/STAT) signal transduction pathway is present and active in meningiomas. The results of these investigations are important for all meningioma therapies that, similar to interferon-alpha-2B (IFNalpha-2B), depend on activation of this pathway for their effect. The authors were interested in evaluating the importance, if any, of the JAK/STAT pathway in the biology and therapy for these tumors.


METHODS
Total proteins were extracted from 17 meningioma samples and the levels of JAKs and STATs were determined by using Western blot analysis. Levels of these proteins in meningiomas were compared with those found in normal dura. The JAKs and STATs (with the exception of Jak3 and Tyk2) were present 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. Differences in relative levels were found when meningiomas were subdivided according to the current neuropathological criteria and the highest levels were found in transitional meningiomas. The authors also investigated, using tyrosine-phosphorylated Statl and Stat3 antibodies, whether STATs were activated in meningiomas and normal dura in vivo. Their results indicate that both Statl and Stat3 are phosphorylated in vivo in meningiomas and in the dura. Furthermore, in vitro experiments in which two independent short-term cultures obtained from freshly dissected meningioma samples were used indicated that Statl and Stat3 are phosphorylated in response to treatment with IFNalpha-2B. Exposure of meningioma cells to IFNalpha-2B leads to nuclear translocation of tyrosine-phosphorylated Statl and Stat3, as demonstrated by immunocytochemical analysis.


CONCLUSIONS
The results of this study indicate that the JAK and STAT families of proteins are important effectors in brain tumors and support the idea that the effects of IFNalpha in vivo are direct and not mediated by the immune system. This suggests a role for modulation of STAT transcription factors in inhibiting meningioma cell proliferation.
Magrassi
L
L
Neurosurgery Department, Policlinico San Matteo, and Institute of Pharmacology, University of Pavia, Italy.
De-Fraja
C
C
Conti
L
L
Butti
G
G
Infuso
L
L
Govoni
S
S
Cattaneo
E
E
D000209:Acute-Phase Proteins / Q000032:analysis / Q000235:genetics; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D004388:Dura Mater / Q000737:chemistry; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D053613:Janus Kinase 1; D053616:Janus Kinase 3; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000628:therapy; D008579:Meningioma / Q000235:genetics* / Q000628:therapy; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics*; D011506:Proteins / Q000032:analysis / Q000235:genetics; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000235:genetics*; D053634:TYK2 Kinase; D015534:Trans-Activators / Q000032:analysis / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000209:Acute-Phase Proteins; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009363:Neoplasm Proteins; D011506:Proteins; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507933:JAK3 protein, human; D053613:Janus Kinase 1; D053616:Janus Kinase 3; D053634:TYK2 Kinase; C070139:TYK2 protein, human