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

Nicoletta Gagliano, Francesco Costa, Chiara Cossetti, Letizia Pettinari, Rosaria Bassi, Maurizio Chiriva-Internati, Everardo Cobos, Magda Gioia, Stefano Pluchino

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1349-1356
Number of pages8
JournalOncology Reports
Volume22
Issue number6
DOIs
Publication statusPublished - 2009

Keywords

  • Astrocytes
  • Connexin 43
  • Glial fibrillary acidic protein
  • Glioblastoma
  • Matrix metalloproteinase-2
  • Secreted protein acidic and rich in cysteine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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