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Open Access Research article

Identification of a novel set of genes reflecting different in vivo invasive patterns of human GBM cells

Massimiliano Monticone1, Antonio Daga1, Simona Candiani2, Francesco Romeo13, Valentina Mirisola1, Silvia Viaggi12, Ilaria Melloni1, Simona Pedemonte1, Gianluigi Zona1, Walter Giaretti1, Ulrich Pfeffer1 and Patrizio Castagnola1*

Author affiliations

1 IRCCS Azienda Ospedaliera Universitaria San Martino - IST - Istituto Nazionale per la Ricerca sul Cancro, Largo R. Benzi, 10, 16132 Genoa, Italy

2 Dipartimento di Scienze della Terra, dell’Ambiente e della Vita (DISTAV), Università di Genova, Genoa, Italy

3 TibMolbiol, Largo R. Benzi, 10, 16132, Genoa, Italy

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Citation and License

BMC Cancer 2012, 12:358  doi:10.1186/1471-2407-12-358

Published: 17 August 2012

Abstract

Background

Most patients affected by Glioblastoma multiforme (GBM, grade IV glioma) experience a recurrence of the disease because of the spreading of tumor cells beyond surgical boundaries. Unveiling mechanisms causing this process is a logic goal to impair the killing capacity of GBM cells by molecular targeting.

We noticed that our long-term GBM cultures, established from different patients, may display two categories/types of growth behavior in an orthotopic xenograft model: expansion of the tumor mass and formation of tumor branches/nodules (nodular like, NL-type) or highly diffuse single tumor cell infiltration (HD-type).

Methods

We determined by DNA microarrays the gene expression profiles of three NL-type and three HD-type long-term GBM cultures. Subsequently, individual genes with different expression levels between the two groups were identified using Significance Analysis of Microarrays (SAM). Real time RT-PCR, immunofluorescence and immunoblot analyses, were performed for a selected subgroup of regulated gene products to confirm the results obtained by the expression analysis.

Results

Here, we report the identification of a set of 34 differentially expressed genes in the two types of GBM cultures. Twenty-three of these genes encode for proteins localized to the plasma membrane and 9 of these for proteins are involved in the process of cell adhesion.

Conclusions

This study suggests the participation in the diffuse infiltrative/invasive process of GBM cells within the CNS of a novel set of genes coding for membrane-associated proteins, which should be thus susceptible to an inhibition strategy by specific targeting.

Massimiliano Monticone and Antonio Daga contributed equally to this work