human tumor cells induce angiogenesis through positive feedback between cd147 and insulin-like growth factor-i人类肿瘤细胞诱导血管生成通过正反馈cd147和胰岛素样生长因子之间的关系.pdfVIP

Human Tumor Cells Induce Angiogenesis through Positive Feedback between CD147 and Insulin-Like Growth Factor-I 1,2 . 3. 2 2 2 Yanke Chen * , Xingchun Gou , Xia Ke , Hongyong Cui , Zhinan Chen * 1 College of Medicine, Xi’an Jiaotong University, Xi’an, China, 2 Department of Cell Biology Cell Engineering Research Center State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi’an, China, 3 Laboratory of Cell Biology Translational Medicine, Xi’an Medical University, Xi’an, China Abstract Tumor angiogenesis is a complex process based upon a sequence of interactions between tumor cells and endothelial cells. Previous studies have shown that CD147 was correlated with tumor angiogenesis through increasing tumor cell secretion of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). In this study, we made a three- dimensional (3D) tumor angiogenesis model using a co-culture system of human hepatocellular carcinoma cells SMMC-7721 and humanumbilical vein endothelial cells (HUVECs) in vitro. We found that CD147-expressing cancer cells could promote HUVECs to form net-like structures resembling the neo-vasculature, whereas the ability of proliferation, migration and tube formation of HUVECs was significantly decreased in tumor conditioned medium (TCM) of SMMC-7721 cells transfected with specific CD147-siRNA. Furthermore, by assaying the change of pro-angiogenic factors in TCM, we found that the inhibition of CD147 expression led to significant decrease of VEGF and insulin-like growth factor-I (IGF-I) secretion. Interestingly, we also found that IGF-I up-regulated the expression of CD147 in both tumor cells and HUVECs. These findings suggest that there is a positive feedback between