Blockage of Ca(2+)-permeable AMPA receptors suppresses migration and induces apoptosis in human glioblastoma cells.

Ishiuchi, Shogo; Tsuzuki, Keisuke; Yoshida, Yukari; Yamada, Nobuaki; Hagimura, Norikazu; Okado, Haruo; Miwa, Akiko; Kurihara, Hideyuki; Nakazato, Yoichi; Tamura, Masaru; Sasaki, Tomio; Ozawa, Seiji

Ishiuchi, Shogo; Tsuzuki, Keisuke; Yoshida, Yukari; Yamada, Nobuaki; Hagimura, Norikazu; Okado, Haruo; Miwa, Akiko; Kurihara, Hideyuki; Nakazato, Yoichi; Tamura, Masaru; Sasaki, Tomio; Ozawa, Seiji.

Afiliación

Ishiuchi S; Department of Neurosurgery, Gunma University School of Medicine, Maebashi, Gunma, Japan. ishogo@showa.gunma-u.ac.jp

Nat Med ; 8(9): 971-8, 2002 Sep.

Article en En | MEDLINE | ID: mdl-12172541

RESUMEN

Glioblastoma multiforme is the most undifferentiated type of brain tumor, and its prognosis is extremely poor. Glioblastoma cells exhibit highly migratory and invasive behavior, which makes surgical intervention unsuccessful. Here, we showed that glioblastoma cells express Ca(2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptors assembled from the GluR1 and/or GluR4 subunits, and that their conversion to Ca(2+)-impermeable receptors by adenovirus-mediated transfer of the GluR2 cDNA inhibited cell locomotion and induced apoptosis. In contrast, overexpression of Ca(2+)-permeable AMPA receptors facilitated migration and proliferation of the tumor cells. These findings indicate that Ca(2+)-permeable AMPA receptors have crucial roles in growth of glioblastoma. Blockage of these Ca(2+)-permeable receptors may be a useful therapeutic strategy for the prevention of glioblastoma invasion.

Asunto(s)

Neoplasias Encefálicas/patología; Glioblastoma/patología; Receptores AMPA/antagonistas & inhibidores; Adenoviridae/genética; Animales; Apoptosis; Neoplasias Encefálicas/tratamiento farmacológico; Neoplasias Encefálicas/metabolismo; Calcio/metabolismo; Movimiento Celular/genética; Vectores Genéticos/farmacología; Glioblastoma/tratamiento farmacológico; Glioblastoma/metabolismo; Humanos; Imidazoles/farmacología; Ratones; Ratones Desnudos; Permeabilidad; Quinoxalinas/farmacología; Receptores AMPA/efectos de los fármacos; Receptores AMPA/genética; Receptores AMPA/metabolismo; Células Tumorales Cultivadas; Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico/metabolismo; Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico/farmacología

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Receptores AMPA / Glioblastoma Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2002 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos

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