간세포성장인자가 하인두 편평세포암 세포주에서 Matrix Metalloproteinase(MMP)-2, 9과 Urokinase Type Plasmogen Activator에 미치는 영향

Abstract

Background and Objectives：Recent reports revealed that hepatocyte growth factor (HGF) is related to tumor invasion and metastasis. Activation of the urokinase-type plasminogen activator (u-PA)/plasmin proteolytic network and matrix metalloproteinase has been shown to play a key role in tumor invasion and dissemination of various malignancies. So we examined the effect of HGF/c-Met on MMP-2, 9 and u-PA in FaDu cell, a hypopharyngeal squamous cell carcinoma cell line.

Materials and Method：We performed RT-PCR and Western blot in FaDu. Tumor cell invasiveness was assessed by the membrane invasion assay (using Transwell chamber). To examine the role of MMP-2, 9 and the relation between HGF and MMP in the invasion of hypopharyngeal cancer, RT-PCR and zymography were performed in FaDu cells. We tested to confirm the HGF-mediated plasmin activation.

Results：The expressions of c-Met mRNA and protein were detected in the hypopharyngeal cell line while that of HGF was not. HGF markedly enhanced the invasion of cancer cells in a Transwell invasion chamber in a dose-dependent manner (p<0.05). The expression of MMP was detected in hypopharyngeal cancer cells and exogenous HGF slightly enhanced the induction of MMP-2 activity in zymogram analysis. The activity of u-PA was detected in FaDu and HGF (above 10 units/mL) enhanced the activity of u-PA (p<0.05).

Conclusion：These results suggest that HGF may play an important role in hypopharyngeal cancer through the activation of u-PA and matrix metalloproteinase.