title: Modeling NF2 with human arachnoidal and meningioma cell culture systems: NF2 silencing reflects the benign character of tumor growth.
abstract: Meningiomas, common tumors arising from arachnoidal cells of the meninges, may occur sporadically, or in association with the inherited disorder, neurofibromatosis 2 (NF2). Most sporadic meningiomas result from NF2 inactivation, resulting in loss of tumor suppressor merlin, implicated in regulating membrane-cytoskeletal organization. To investigate merlin function in an authentic target cell type for NF2 tumor formation, we established primary cultures from genetically-matched meningioma and normal arachnoidal tissues. Our studies revealed novel and distinct cell biological and biochemical properties unique to merlin-deficient meningioma cells compared to merlin-expressing arachnoidal and meningioma cells, and other NF2-deficient cell types. Merlin-deficient meningioma cells displayed cytoskeletal and cell contact defects, altered cell morphology and growth properties, most notably cell senescence, implicating the activation of senescence pathways in limiting benign meningioma growth. Merlin suppression by RNAi in arachnoidal cells replicated merlin-deficient meningioma features, thus establishing these cell systems as disease-relevant models for studying NF2 tumorigenesis.
authors.affiliation: Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Richard B. Simches Research Building, 185 Cambridge Street, Boston, MA 02114, USA.
authors.forename: Marianne F
authors.initials: MF
authors.lastname: James
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Lelke
authors.forename: Mia
authors.initials: M
authors.lastname: Maccollin
authors.forename: Scott R
authors.initials: SR
authors.lastname: Plotkin
authors.forename: Anat O
authors.initials: AO
authors.lastname: Stemmer-Rachamimov
authors.forename: Vijaya
authors.initials: V
authors.lastname: Ramesh
authors.forename: James F
authors.initials: JF
authors.lastname: Gusella
mesh_terms: D000199:Actins / Q000378:metabolism; D001099:Arachnoid / Q000166:cytology* / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D051177:Catenins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D016515:Genes, Neurofibromatosis 2 / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008577:Meningeal Neoplasms / Q000473:pathology*; D008579:Meningioma / Q000473:pathology*; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism; D025581:Neurofibromin 2 / Q000172:deficiency; D034741:RNA, Small Interfering / Q000494:pharmacology*
chemical_list: D000199:Actins; D051177:Catenins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D025581:Neurofibromin 2; D034741:RNA, Small Interfering; D001973:Bromodeoxyuridine