Chen Yanke, Gou Xingchun, Kong Derek Kai, Wang Xiaofei, Wang Jianhui, Chen Zeming, Huang Chen, Zhou Jiangbing
Experiment Center of Biomedical Research School of Medicine, Xi'an Jiaotong University, Xi'an 710061, P. R. China.
Department of Neurosurgery, Yale University, New Haven, CT 06511, USA.
Oncotarget. 2015 Oct 20;6(32):32575-85. doi: 10.18632/oncotarget.5331.
EMMPRIN, a cell adhesion molecule highly expressed in a variety of tumors, is associated with poor prognosis in cancer patients. Mechanistically, EMMPRIN has been characterized to contribute to tumor development and progression by controlling the expression of MMPs and VEGF. In the present study, by using fluorescently labeled bone marrow-derived cells (BMDCs), we found that the down-regulation of EMMPRIN expression in cancer cells reduces tumor growth and metastasis, and is associated with the reduced recruitment of BMDCs. Further protein profiling studies suggest that EMMPRIN controls BMDC recruitment through regulating the secretion of soluble factors, notably, VEGF and SDF-1. We demonstrate that the expression and secretion of SDF-1 in tumor cells are regulated by EMMPRIN. This study reveals a novel mechanism by which EMMPRIN promotes tumor growth and metastasis by recruitment of BMDCs through controlling secretion and paracrine signaling of SDF-1 and VEGF.
细胞外基质金属蛋白酶诱导因子（EMMPRIN）是一种在多种肿瘤中高表达的细胞黏附分子，与癌症患者的不良预后相关。从机制上讲，EMMPRIN的特征在于通过控制基质金属蛋白酶（MMPs）和血管内皮生长因子（VEGF）的表达来促进肿瘤发展和进展。在本研究中，通过使用荧光标记的骨髓来源细胞（BMDCs），我们发现癌细胞中EMMPRIN表达的下调会减少肿瘤生长和转移，并与BMDCs募集的减少有关。进一步的蛋白质谱研究表明，EMMPRIN通过调节可溶性因子（特别是VEGF和基质细胞衍生因子-1（SDF-1））的分泌来控制BMDCs的募集。我们证明肿瘤细胞中SDF-1的表达和分泌受EMMPRIN调节。本研究揭示了一种新机制，即EMMPRIN通过控制SDF-1和VEGF的分泌及旁分泌信号募集BMDCs，从而促进肿瘤生长和转移。
