Journal
ONCOLOGY REPORTS
Volume 22, Issue 6, Pages 1349-1356Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or_00000574
Keywords
glioblastoma; astrocytes; glial fibrillary acidic protein; connexin 43; matrix metalloproteinase-2; secreted protein acidic and rich in cysteine
Categories
Funding
- Fundacao para a Ciencia e a Tecnologia (FCT) [SFRH/BD/15899/2005]
- Italian Multiple Sclerosis Foundation (FISM) [2004/R/15]
- National Multiple Sclerosis Society (NMSS) [RG-4001A1]
- Banca Agricola Popolare di Ragusa (BAPR)
- Fundação para a Ciência e a Tecnologia [SFRH/BD/15899/2005] Funding Source: FCT
Ask authors/readers for more resources
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-beta 1 (TGF-beta 1), secreted protein acidic and rich in cysteine (SPARC), and connexin 43 (CX43). co-cultures of human neural stern 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-beta 1 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available