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Biological role of HGF/MET pathway in renal cell carcinoma
1Department of Urology, University of Tokyo, National Cancer Center Hospital, Japan.
Purpose:
Several lines of evidence show that hepatocyte growth factor (HGF) and its receptor MET play a significant role in the progression of various cancers including renal cell carcinoma (RCC). Our objectives were to evaluate the gene expression of HGF and MET in RCC, and to examine the effect of HGF on the biological activities of cultured RCC cells.
Materials And Methods:
We examined the gene expression of HGF and MET in 27 primary RCC tumors by quantitative competitive RT-PCR. The effects of HGF on in vitro chemoinvasion assay and the expression of matrix metalloproteinase-9 (MMP-9), and the induction of Fas-induced apoptosis were studied by transfection of HGF cDNA to cultured RCC cells, Caki-1.
Results:
HGF mRNA and MET mRNA were detected in all surgical specimens. The level of expressed HGF mRNA was proportional with the volume of tumor (r = 0.50, p = 0.015). Caki-1 cells overexpressing HGF cells showed enhanced in vitro invasiveness in the chemoinvasion assay and increased activity of 92 kDa type IV collagenase (MMP-9). The sensitivity to Fas-induced cell death was reduced in HGF transfectants, which was reversed by the presence of anti-HGF antibody.
Conclusions:
HGF enhanced the invasive properties of cultured RCC cells and inhibited Fas-induced apoptosis in vitro. Both HGF and MET mRNA were expressed in RCC tissues tested. Our results indicate that HGF/MET pathway may have a significant role in the progression of RCC.
Insights
Hepatocyte growth factor (HGF) and its receptor MET are expressed in renal cell carcinoma (RCC). HGF enhances RCC cell invasion and inhibits apoptosis, suggesting a role in cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Hepatocyte growth factor (HGF) and its receptor MET are implicated in the progression of various cancers.
- Their specific role in renal cell carcinoma (RCC) warrants further investigation.
Purpose of the Study:
- To evaluate the gene expression of HGF and MET in RCC tissues.
- To examine the impact of HGF on the biological activities of cultured RCC cells.
Main Methods:
- Quantitative competitive RT-PCR was used to assess HGF and MET gene expression in 27 primary RCC tumors.
- HGF cDNA was transfected into Caki-1 RCC cells to study effects on chemoinvasion, matrix metalloproteinase-9 (MMP-9) expression, and Fas-induced apoptosis.
Main Results:
- HGF and MET mRNA were detected in all RCC specimens, with HGF mRNA levels correlating with tumor volume.
- Overexpression of HGF in Caki-1 cells led to increased invasiveness and MMP-9 activity.
- HGF overexpression reduced sensitivity to Fas-induced apoptosis, an effect reversed by anti-HGF antibody.
Conclusions:
- HGF enhances the invasive potential of RCC cells and inhibits Fas-induced apoptosis in vitro.
- Both HGF and MET are expressed in RCC tissues.
- The HGF/MET pathway is likely a significant factor in RCC progression.