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Expression of HPA in astrocytomas and its effect on invasiveness of tumor cells

Yusong Bian, Li Guo, Weiguang Chen, Dan Sheng, Zengbin Lin, Fanqiang Kong, Wenhu Li, Yongan Chen

Objective: To observe the expression of heparanase (HPA) in human astrocytomas tissue and its effect on invasiveness of tumor cells.

Methods: Immunohistochemical Elivision™plus two step method and Realtime-PCR method were used to detect the expression of HPA protein and mRNA in 75 cases of astrocytoma tissues and 40 cases of normal brain tissues. Silencing HPA expression in astrocytoma U87 cells by siRNA interference technique, and adopting Realtime PCR, Western blot, Transwell chamber experiment, the expression and cell invasiveness change of tumor cells HPA, vascular endothelial growth factor (VEGF), matrix metalloproteinase -9 (MMP.9) were detected.

Results: The expression of HPA protein was not found in normal brain tissues, HPA positive expression rate in astrocytoma tissues was 78.67% (59/75), and the positive expression rate of HPA in astrocytoma tissues was significantly higher than that in normal brain tissues, and its expression level of mRNA was significantly higher than that in normal brain tissues, the difference of which was statistically significant (χ²=67.8, P<0.05). The positive expression rate of HPA in grade II to IV group of astrocytoma increased gradually, the difference of which was statistically significant (χ²=131.5, P<0.05); the positive expression rate of HPA in metastasis group was significantly higher than that in non-metastasis group (χ²=89.3, P<0.05). SiRNA can effectively inhibit the expression of HPA in astrocytoma U87 cells, and down regulate the expression of VEGF, MMP-9, at the same time the number of transmembrane cells decreased significantly, and the difference was statistically significant (P<0.05).

Conclusion: HPA is highly expressed in astrocytomas tissues, and with the increase of malignancy of tumor, the expression increases gradually. The cell invasiveness decreased significantly after siRNA silenced HPA, and HPA might be a potential target for the treatment of astrocytomas.