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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line, Tumor
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Cell Movement / physiology*
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Chondrosarcoma / enzymology*
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Chondrosarcoma / genetics
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Chondrosarcoma / physiopathology*
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Hepatocyte Growth Factor / physiology*
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Humans
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Matrix Metalloproteinase 2 / genetics
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Matrix Metalloproteinase 2 / metabolism
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NF-kappa B / metabolism
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Neoplasm Invasiveness / physiopathology
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Phosphatidylinositol 3-Kinases / metabolism
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Protein Kinase C / metabolism
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Proto-Oncogene Proteins c-akt / metabolism
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Proto-Oncogene Proteins c-met / antagonists & inhibitors
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Proto-Oncogene Proteins c-met / genetics
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Proto-Oncogene Proteins c-met / physiology*
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Signal Transduction / genetics
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Up-Regulation / genetics
Substances
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HGF protein, human
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NF-kappa B
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Hepatocyte Growth Factor
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Phosphatidylinositol 3-Kinases
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protein kinase C gamma
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Proto-Oncogene Proteins c-met
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Proto-Oncogene Proteins c-akt
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Protein Kinase C
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MMP2 protein, human
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Matrix Metalloproteinase 2
Grants and funding
This study was supported by grants from the National Science Council of Taiwan (NSC99-2320-B-039-003-MY3 and NSC100-2320-B-039-028-MY3) and China Medical University Hospital (DMR-102-055). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.