title: HGF and c-Met interaction promotes migration in human chondrosarcoma cells.
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.
authors: Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan.
authors: Hsi-Kai
authors: HK
authors: Tsou
authors: Hsien-Te
authors: HT
authors: Chen
authors: Ya-Huey
authors: YH
authors: Hung
authors: Chia-Hao
authors: CH
authors: Chang
authors: Te-Mao
authors: TM
authors: Li
authors: Yi-Chin
authors: YC
authors: Fong
authors: Chih-Hsin
authors: CH
authors: Tang
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D002813:Chondrosarcoma / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology*; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: C066855:HGF protein, human; D016328:NF-kappa B; D017228:Hepatocyte Growth Factor; D019869:Phosphatidylinositol 3-Kinases; C087857:protein kinase C gamma; D019859:Proto-Oncogene Proteins c-met; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2