title: CIP2A and PP2A in human leptomeninges, arachnoid granulations and meningiomas.
abstract: Previously we have found that mitogens stimulate proliferation of meningioma cells of all grades, in part, by activation of the PI3K-PKB/Akt-PRAS40-mTOR pathway regulated to some degree by the tumor suppressor phosphatase PP2A. PP2A activity is inhibited by the oncoprotein cancerous inhibitor of PP2A (CIP2A), which has not been studied in meningiomas to our knowledge. Six fetal and one adult human leptomeningeal samples and 38 meningiomas were evaluated by western blot. Fifteen adult arachnoid granulations and 58 formalin-fixed meningiomas (36 World Health Organization grade I, 15 grade II and seven grade III) were evaluated by immunohistochemistry. The effects of the mitogens platelet derived growth factor-BB (PDGF-BB) and cerebrospinal fluid on CIP2A were also studied. By western blot, CIP2A and PP2A were found in the five fetal and one adult leptomeninges and all meningiomas. By immunohistochemistry, CIP2A was detected in the arachnoid granulations and all meningiomas. CIP2A tended to be higher in grade III tumors. Three fetal leptomeningeal (two grade I and one grade II) and meningioma cells treated with PDGF-BB and/or human cerebrospinal fluid resulted in a slight increase in CIP2A in the leptomeningeal cells but not meningioma cells. Considered the mechanism of action and seen in other neoplasms, these findings raise the possibility that CIP2A may participate in the biology of meningiomas.
authors.affiliation: Department of Pathology, Division of Neuropathology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 626, Rochester, NY 14623, USA. Electronic address: mahlon_johnson@urmc.rochester.edu.
authors.forename: Mahlon D
authors.initials: MD
authors.lastname: Johnson
authors.affiliation: Department of Urology, State University of New York, Upstate Medical University, Syracuse, NY, USA.
authors.forename: Jay E
authors.initials: JE
authors.lastname: Reeder
authors.affiliation: Department of Pathology, Division of Neuropathology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 626, Rochester, NY 14623, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: O'Connell
authors.affiliation: Department of Urology, State University of New York, Upstate Medical University, Syracuse, NY, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Woodford
authors.affiliation: Department of Pathology, Division of Neurosurgery, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Walter
mesh_terms: D000368:Aged; D001324:Autoantigens / Q000378:metabolism*; D000077214:Becaplermin; D015153:Blotting, Western; D002478:Cells, Cultured; D002555:Cerebrospinal Fluid / Q000378:metabolism; D005260:Female; D005333:Fetus; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008578:Meninges / Q000378:metabolism* / Q000473:pathology; D008579:Meningioma / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D060787:Neoplasm Grading; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism
chemical_list: D001324:Autoantigens; C500266:CIP2A protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D054648:Protein Phosphatase 2
keywords: Arachnoid granulations; CIP2A; Leptomeninges; Meningioma; PP2A