SERPINA3 induced by astroglia/microglia co-culture facilitates glioblastoma stem-like cell invasion.

ABSTRACT

Glioblastoma (GBM) is a highly invasive and malignant brain tumor. Currently, it remains unclear whether Glioblastoma stem-like cells (GSCs) contribute to the invasive phenotype of GBM. Invasion is a complex process involving interactions between tumor cells with the extracellular matrix (ECM), in addition to normal cells. The present study aimed to identify the regulators of GSCs invasion in the GBM tumor microenvironment. An integrative analysis was conducted to identify genes that are important for GSC invasion and are specifically upregulated in astroglia/microglia co-cultured GSCs. Of the identified genes, serpin peptidase inhibitor clade A member 3 (SERPINA3) was observed to be abnormally overexpressed in astroglia/microglia co-cultured GSCs. To further investigate the role of SERPINA3 in glioma pathogenesis and prognosis, a tissue microarray analysis was conducted to evaluate the expression of SERPINA3 and its association to clinicopathological factors and patient survival. The data indicated that upregulation of SERPINA3 was significantly associated with glioma progression and poor patient survival. Furthermore, it was demonstrated that the upregulation of SERPINA3 in glioma may contribute to the invasive behavior of GBM cells by remodeling of the ECM. Overall, the findings of the present study may be useful in future prognosis of GBM patients, suggesting that SERPINA is a potential therapeutic target, and may lead to further understanding of GBM and cancer progression as a whole.