Etiology and Pathogenesis > Invasion

Meeting Abstract

Pharmacological Blockage of Mglu2/3 Metabotropic Glutamate Receptors Reduces Cell Proliferation of Human Glioma Cells in Vitro and in Vivo

Antionetta Arcella, Mara D’Onofrio, Valeria Bruno, Richard T. Ngomba, Giuseppe Battaglia, Felice Giangaspero, and Ferdinando Nicoletti

Istituto Neurologico Mediterraneo Neuromed, Pozzilli, Italy; University of Rome La Sapienza, Rome, Italy

Glial cell proliferation culture is under the control of metabotropic glutamate (mGlu) receptors (Ciccarelli et al., 1997).
Recent studies have disclosed the role of individual mGlu receptor subtypes in the control of glial cell proliferation.
Using subtype-selective mGlu recepton agonists, Cicaralli et al. (1997) have shown that pharmacological activation of mGlu5 receptors increases DNA synthesis in cultured astrocytes, whereas activation of mGlu3 receptors produces the opposite effect.
We have extended the study to human glioma cells in primary cultures.
An initial screening of primary cultures from bioptic samples of human glioblastomas showed that half of the cultures expressed mGlu3 receptors.
In 3 cultures expressing mGlu2/3 receptors, addition of the agonist LY341495 (1 μM) slowed the rate of cell growth as assessed by [methyl-³H]-thymidine incorporation or serial cell count.
The antiproliferative effect was detected during the linear phase of cell growth as well as in cultures arrested in G0 and then stimulated to proliferate by serum or epidermal growth factor.
Under the latter condition, LT341495 was also able to reduce the increase in cyclin D1 expression in cells committed to proliferate.
This effect was reverted by co-addition of the patent agonist LY379268.
Preliminary data in vivo suggest that LY341495 (1 mg/kg) also reduces tumor growth in nude mice subcutaneously inoculated with continuous human glioma cell line U87 MG, which similarly expressed mGlu2/3.

Copyright © 2003 by the Society for Neuro-Oncology