© 2006 by the Society for Neuro-Oncology
Expression studies in gliomas and glial cells do not support a tumor suppressor role for LGI11
Department of Experimental Research and Diagnostics, Istituto Nazionale Neurologico C. Besta, Milan 20133, Italy (T.P., E.L., B.S.-M., P.L.P., B.O., R.M., F.I., C.F., G.F.); Institut für Rekonstruktive Neurobiologie, University of Bonn, Life and Brain Center and Hertie Foundation, 53105 Bonn, Germany (C.J., O.B.); Institute of Human Genetics, Ludwig Maximilians University Munich, University Hospital, Munich 80336, Germany (W.G., O.S.); Department of Anatomy and Cell Biology, University of Bergen, Bergen N-5009, Norway (D.G., J.W., R.B.); Department of Pharmacology, University of Milan, Milan 20129, Italy (M.G.C., L.M.V.)
3 Address correspondence to Gaetano Finocchiaro, Istituto Nazionale Neurologico Besta, via Celoria 11, 20133 Milan, Italy (finocchiaro{at}istituto-besta.it).
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Abstract |
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Disruptions of LGI1 in glioblastoma (GBM) cell lines and LGI1 mutations in families with autosomal dominant epilepsy imply a role for LGI1 in glial cells as well as in neurons. Although we and others could not find LGI1 mutations in malignant gliomas, our initial studies appeared to support the idea that LGI1 is poorly expressed or absent in these tumors. Microarray data suggested that LGI1 could be involved in the control of matrix metalloproteinases, and we found that tumors derived from U87 glioblastoma cells overexpressing LGI1 were less aggressive than U87 control tumors. To our surprise, we observed that LGI1 expression after differentiation of murine neural stem cells was robust in neurons but negligible in glial cells, in agreement with immunohistochemistry studies on rodent brain. This observation could suggest that the variable levels of LGI1 expression in gliomas reflect the presence of neurons entrapped within the tumor. To test this hypothesis, we investigated LGI1 expression in parallel with expression of the neuronal marker NEF3 by real-time PCR on 30 malignant gliomas. Results showed a strong, positive correlation between the expression levels of these two genes (P < 0.0001). Thus, our data confirm that LGI1 is involved in cell-matrix interactions but suggest that its expression is not relevant in glial cells, implying that its role as a tumor suppressor in gliomas should be reconsidered.
Keywords: epilepsy, glioma, invasion, metalloproteinase, migration, tumor suppressor gene
Received September 17, 2005; Accepted October 26, 2005
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