HGF and c-Met interaction promotes migration in human chondrosarcoma cells.

Hsi-Kai Tsou,Chih-Hsin Tang,Yi-Chin Fong,Ya-Huey Hung,Te-Mao Li,Chia-Hao Chang,Hsien-Te Chen,Rajeev Samant

doi:10.1371/journal.pone.0053974

Abstract

Chondrosarcoma is a type of highly malignant tumor with a potent capacity for local invasion and causing distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. Hepatocyte growth factor (HGF) has been demonstrated to stimulate cancer proliferation, migration, and metastasis. However, the effect of HGF on migration activity of human chondrosarcoma cells is not well known. Here, we found that human chondrosarcoma tissues demonstrated significant expression of HGF, which was higher than that in normal cartilage. We also found that HGF increased the migration and expression of matrix metalloproteinase (MMP)-2 in human chondrosarcoma cells. c-Met inhibitor and siRNA reduced HGF-increased cell migration and MMP-2 expression. HGF treatment resulted in activation of the phosphatidylinositol 3′-kinase (PI3K)/Akt/PKCδ/NF-κB pathway, and HGF-induced expression of MMP-2 and cell migration was inhibited by specific inhibitors or siRNA-knockdown of PI3K, Akt, PKCδ, and NF-κB cascades. Taken together, our results indicated that HGF enhances migration of chondrosarcoma cells by increasing MMP-2 expression through the c-Met receptor/PI3K/Akt/PKCδ/NF-κB signal transduction pathway.

Highlights

Hepatocyte growth factor (HGF) was identified in the early 1980s [1,2] and was subsequently determined to be a heterodimeric molecule composed of an alpha and beta chain [3]
We found that the expression of HGF in tissue from chondrosarcoma patients was significantly higher than in normal cartilage (Fig. 1A, arrow shows the HGF staining)
To elucidate a link between HGF expression and chondrosarcoma cell migration, we examined the migratory activity of human chondrosarcoma by using the Transwell assay

Summary

Introduction

Hepatocyte growth factor (HGF) was identified in the early 1980s [1,2] and was subsequently determined to be a heterodimeric molecule composed of an alpha and beta chain [3]. HGF has been reported to play critical roles in proliferation, migration, invasion, tumor angiogenesis, and lymphangiogenesis, recently [4,5]. High circulating HGF levels are associated with lower survival and development of distant metastasis, and increases in circulating HGF are correlated with tumor size, nodal status, and histological evidence of venous invasion [9,10]. These data suggest that HGF plays a critical role during cancer migration and metastasis

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Results

Conclusion