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Expression of hepatocyte growth factor and matrix metalloproteinase-2 in human glioma
1Department of Neurosurgery, Gifu University School of Medicine, Japan. hirohito@cc.gifu-u.ac.jp
Abstract:
Hepatocyte growth factor (HGF) has a stimulatory effect on the synthesis of matrix metalloproteinase-2 (MMP-2), which is involved in glioma invasion. In this study, to clarify the correlation between the expression of HGF and MMP-2 in glioma tissues, immunohistochemical analysis of HGF and MMP-2 was performed in 11 cases of astrocytoma, 10 cases of anaplastic astrocytoma, and 9 cases of glioblastoma. As a result, expression of HGF and MMP-2 was correlated with the grade of malignancy (P = 0.0181 and 0.0001, respectively), and a significant correlation between the immunoreactivity of HGF and that of MMP-2 was observed (P < 0.05). Immunofluorescence study revealed the concomitant expression of HGF and MMP-2 in glioma tissue. In cultured glioma cell lines (SNB-19, U87MG, and U373MG), exogenous recombinant HGF effectively acted on the production of the active and latent forms of MMP-2 protein in a dose-dependent manner. Active MMP-2 increased more effectively than the latent form. Taken together, these results suggest that HGF may promote glioma invasion in vivo by production of MMP-2.
Insights
Hepatocyte growth factor (HGF) stimulates matrix metalloproteinase-2 (MMP-2) production, promoting glioma invasion. This study found HGF and MMP-2 expression correlate with glioma malignancy, suggesting HGF drives invasion via MMP-2.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cancer Research
Background:
- Glioma invasion is a critical factor in patient prognosis.
- Matrix metalloproteinase-2 (MMP-2) is implicated in extracellular matrix degradation and tumor cell migration.
- Hepatocyte growth factor (HGF) is known to influence cell growth and motility.
Purpose of the Study:
- To investigate the correlation between Hepatocyte growth factor (HGF) and matrix metalloproteinase-2 (MMP-2) expression in glioma tissues.
- To determine if HGF influences MMP-2 production in glioma cells.
- To elucidate the role of HGF-MMP-2 interaction in glioma invasion.
Main Methods:
- Immunohistochemical analysis of HGF and MMP-2 in 11 astrocytomas, 10 anaplastic astrocytomas, and 9 glioblastomas.
- Immunofluorescence studies to assess concomitant expression of HGF and MMP-2.
- In vitro experiments using cultured glioma cell lines (SNB-19, U87MG, U373MG) treated with recombinant HGF.
Main Results:
- HGF and MMP-2 expression levels significantly correlated with glioma grade of malignancy (P = 0.0181 and P = 0.0001, respectively).
- A significant positive correlation was observed between HGF and MMP-2 immunoreactivity in glioma tissues (P < 0.05).
- Exogenous HGF treatment dose-dependently increased the production of both active and latent forms of MMP-2 in cultured glioma cells, with a more pronounced effect on active MMP-2.
Conclusions:
- HGF expression is closely associated with the malignancy grade of gliomas.
- HGF directly stimulates MMP-2 production in glioma cells.
- These findings suggest that HGF plays a key role in promoting glioma invasion through the induction of MMP-2.