Glioma-astrocyte interaction modifies the astrocyte phenotype in a co-culture experimental model

  • Authors:
    • Nicoletta Gagliano
    • Francesco Costa
    • Chiara Cossetti
    • Letizia Pettinari
    • Rosaria Bassi
    • Maurizio Chiriva-Internati
    • Everardo Cobos
    • Magda Gioia
    • Stefano Pluchino
  • View Affiliations

  • Published online on: December 1, 2009     https://doi.org/10.3892/or_00000574
  • Pages: 1349-1356
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Abstract

As the majority of gliomas arise through malignant transformation of astrocytes, we aimed at investigating the interaction between malignant glioma cells and astrocytes in a co-culture experimental model. For this purpose we analyzed the expression of genes and proteins involved in tumor promotion and invasion, such as glial fibrillary acidic protein (GFAP), matrix metalloproteinase-2 (MMP-2), tissue inhibitor of MMP-2 (TIMP-2), transforming growth factor-β1 (TGF-β1), secreted protein acidic and rich in cysteine (SPARC), and connexin 43 (CX43). Co-cultures of human neural stem cell-derived astrocytes and U87 MG astrocytoma cells were performed in a transwell system. Gene expression was evaluated by real-time RT-PCR, and protein analysis was performed by Western blotting, SDS-zymography, and immunofluorescence. GFAP tended to be up-regulated in astrocytes co-cultivated with U87, suggesting a reactive response induced by glioma cells. CX43 mRNA tended to be down- regulated in co-cultured astrocytes, as well as the non-phosphorylated isoform at the protein level. MMP-2 mRNA tended to be up-regulated, and MMP-2 protein levels were significantly increased in astrocytes co-cultivated with U87. TIMP-2 and SPARC mRNA decreased in astrocytes co-cultivated with U87, showing lower expression in glioma cells. By contrast, SPARC protein expression was strongly induced in supernatants of co-cultured astrocytes. TGF-β1 was not modified. Our results suggest that U87 cells elicit phenotype modifications in the neighbouring resident astrocytes very likely mediated by soluble factors. Glioma/astrocyte interaction could possibly trigger an astrocyte phenotype modification consistent with a malignant transformation, and favouring a more permissive environment for glioma cells invasion.

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December 2009
Volume 22 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Gagliano N, Costa F, Cossetti C, Pettinari L, Bassi R, Chiriva-Internati M, Cobos E, Gioia M and Pluchino S: Glioma-astrocyte interaction modifies the astrocyte phenotype in a co-culture experimental model . Oncol Rep 22: 1349-1356, 2009
APA
Gagliano, N., Costa, F., Cossetti, C., Pettinari, L., Bassi, R., Chiriva-Internati, M. ... Pluchino, S. (2009). Glioma-astrocyte interaction modifies the astrocyte phenotype in a co-culture experimental model . Oncology Reports, 22, 1349-1356. https://doi.org/10.3892/or_00000574
MLA
Gagliano, N., Costa, F., Cossetti, C., Pettinari, L., Bassi, R., Chiriva-Internati, M., Cobos, E., Gioia, M., Pluchino, S."Glioma-astrocyte interaction modifies the astrocyte phenotype in a co-culture experimental model ". Oncology Reports 22.6 (2009): 1349-1356.
Chicago
Gagliano, N., Costa, F., Cossetti, C., Pettinari, L., Bassi, R., Chiriva-Internati, M., Cobos, E., Gioia, M., Pluchino, S."Glioma-astrocyte interaction modifies the astrocyte phenotype in a co-culture experimental model ". Oncology Reports 22, no. 6 (2009): 1349-1356. https://doi.org/10.3892/or_00000574