An Odd Couple: MGluR4 And Medulloblastoma

Glutamate receptors don't seem like your everyday target for new anti-cancer drugs. However, biology can be stranger than fiction. In this week's Journal, Iacovelli et al. examined the expression of the group III metabotropic glutamate receptor mGluR4, which is normally expressed on various nerve terminals as well as in cerebellar granule cell precursors. Because the childhood tumor medulloblastoma originates from progenitor cells in the cerebellar external granule layer, the authors looked for mGluR4 expression in the tumor cells. The receptor was expressed in 75% of a sample of medulloblastomas and in several medulloblastoma cell lines. The mGlur4-positive allosteric modulator PHCCC [N-phenyl-7-(hydroxyimino) cyclopropachromen-1a-carboxamide] reduced DNA synthesis and cell proliferation in cell lines and reduced tumor growth in nude mice implanted with medulloblastoma cells. The antigrowth activity of mGluR4 activation appeared to be mediated by inhibition of adenylyl cyclase and decreased activity of the phosphoinositol-3-kinase pathway.

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Luisa Iacovelli, Antonietta Arcella, Giuseppe Battaglia, Simonetta Pazzaglia, Eleonora Aronica, Paola Spinsanti, Alessandra Caruso, Enrico De Smaele, Anna Saran, Alberto Gulino, Mara D'Onofrio, Felice Giangaspero, and Ferdinando Nicoletti

Source: News tips from the Journal of Neuroscience

Contact: Sara Harris
Society for Neuroscience
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An Odd Couple: MGluR4 And Medulloblastoma