Thrombin enhanced migration and MMPs expression of human chondrosarcoma cells involves PAR receptor signaling pathway |
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| Authors: | Hsien‐Te Chen Hsi‐Kai Tsou Chun‐Hao Tsai Chien‐Chung Kuo Yi‐Kai Chiang Chia‐Hao Chang Yi‐Chin Fong Chih‐Hsin Tang |
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| Institution: | 1. Department of Orthopaedic, China Medical University Hospital, Taichung, Taiwan;2. Department of Materials Science and Engineering, Feng Chia University, Taichung, Taiwan;3. Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan;4. Center for General Education, Jen‐Teh Junior College of Medicine, Nursing and Management, Miaoli County, Taiwan;5. School of Chinese Medicine, China Medical University, Taichung, Taiwan;6. Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan;7. Department of Pharmacology, China Medical University, Taichung, Taiwan |
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| Abstract: | Thrombin is a multifunctional protease that can activate hemostasis and coagulation through the cleavage of fibrinogen to form fibrin clots. Thrombin also plays a crucial role in migration and metastasis of human cancer cells. However, the effect of thrombin on migration activity in human chondrosarcoma cells is mostly unknown. Here, we found that thrombin increased the migration and expression of matrix metalloproteinase (MMP)‐2 and MMP‐13 in human chondrosarcoma cells (JJ012 and SW1353 cells). By using pharmacological inhibitors or activators or genetic inhibition by the protease‐activated receptor (PAR), we found that the PAR1 and PAR4 receptor but not PAR3 receptor are involved in thrombin‐mediated cell migration and MMPs expression. Thrombin‐mediated migration and MMPs up‐regulation was attenuated by phospholipase C (PLC), protein kinase C, and c‐Src inhibitor. Activations of PLCβ, PKCα, c‐Src, and NF‐κB pathways after thrombin treatment was demonstrated, and thrombin‐induced MMPs expression and migration activity was inhibited by the specific inhibitors and mutants of PLC, PKC, c‐Src, and NF‐κB cascades. Taken together, our results indicated that thrombin enhances the migration of chondrosarcoma cells by increasing MMP‐2 and MMP‐13 expression through the PAR/PLC/PKCα/c‐Src/NF‐κB signal transduction pathway. J. Cell. Physiol. 223:737–745, 2010. © 2010 Wiley‐Liss, Inc. |
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