[Frontiers in Bioscience 17, 2541-2549, June 1, 2012]

BMP2 Induces PANC-1 cell invasion by MMP-2 overexpression through ROS and ERK

Jun Liu1, Qi-Wen Ben2, Wei-Yan Yao1, Jian-Jun Zhang3, Da-Fan Chen4, Xiang-Yi He1, Lei Li4, Yao-Zong Yuan1

1Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, China; 2Department of Gastroenterology, Changhai Hospital of Second Military Medical University, Shanghai, China; 3Department of Biochemistry and Molecular Biology, Shanghai Jiaotong University School of Medicine,Shanghai, China; 4Department of Gastroenterology, The First People's Hospital, Shanghai Jiaotong University, Shanghai, China


1. Abstract
2. Introduction
3. Materials and methods
3.1. Antibodies and reagents
3.2. Cell culture
3.3. Western blotting
3.4. MMP-2 activity assay
3.5. Invasion assay
3.6. ROS production
3.7. Statistical analysis
4. Results
4.1. BMP2 increases MMP-2 secretion and activity in PANC-1 cells
4.2. BMP2-stimulated ROS activity induces EMT and increases cell invasion in PANC-1 cells
4.3. BMP2-stimulated ROS increases MMP-2 expression and activity in PANC-1 cells
4.4. ERK mediated MMP-2 activity and cell invasion in BMP2-stimulated PANC-1 cells
5. Discussion
6. Acknowledgements
7. References


The emerging roles of bone morphogenetic proteins (BMPs) in the initiation and progression of multiple cancers have drawn great attention in cancer research. We hypothesized that BMP2 promotes cancer metastasis by modulating MMP-2 secretion and activity through intracellular ROS regulation and ERK activation in human pancreatic cancer. Our data showed that stimulation of PANC-1 cells with BMP2 induced MMP-2 secretion and activation, associated with decreased E-cadherin expression, resulting in epithelial-to-mesenchymal transformation (EMT) and cell invasion. Blockade of ROS by the ROS scavenger, 2-MPG, abolished cell invasion, inhibited the EMT process and decreased MMP-2 expression, suggesting ROS accumulation caused an increase in MMP-2 expression in BMP2-stimulated PANC-1 cell invasion. Furthermore, treatment of PANC-1 cells with 2-MPG or ERK inhibitor PD98059 reduced the phosphorylation of ERK, resulting in attenuation of BMP2-induced cell invasion and MMP-2 activation. Taken together, these results suggest that BMP2 induces the cell invasion of PANC-1 cells by enhancing MMP-2 secretion and acting through ROS accumulation and ERK activation.