BMP2 Induces PANC-1 cell invasion by MMP-2 overexpression through ROS and ERK
BMP2 Induces PANC-1 cell invasion by MMP-2 overexpression through ROS and ERK
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DOI：
10.2741/4069
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发表时间：
2012-06-01
影响因子：
3.1
通讯作者：
Yuan, Yao-Zong
中科院分区：
文献类型：
--
作者：
Liu, Jun;Ben, Qi-Wen;Yuan, Yao-Zong
骨形态发生蛋白（BMPs）在多种肿瘤的发生和发展中的作用已引起肿瘤研究的极大关注。我们假设BMP 2通过调节人胰腺癌细胞内ROS的调节和ERK的激活来调节MMP-2的分泌和活性，从而促进肿瘤转移。我们的数据表明，刺激PANC-1细胞与BMP-2诱导MMP-2的分泌和激活，与E-cadherin表达减少，导致上皮间质转化（EMT）和细胞侵袭。通过ROS清除剂2-MPG阻断ROS，消除细胞侵袭，抑制EMT过程并降低MMP-2表达，表明在BMP 2刺激的PANC-1细胞侵袭中，ROS积累导致MMP-2表达增加。此外，用2-MPG或ERK抑制剂PD 98059处理PANC-1细胞减少ERK的磷酸化，导致BMP 2诱导的细胞侵袭和MMP-2活化的减弱。综上所述，这些结果表明，BMP 2诱导PANC-1细胞的细胞侵袭，通过增强MMP-2的分泌，并通过ROS积累和ERK激活的作用。
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.