Disruption of tumor cell adhesion promotes angiogenic switch and progression to micrometastasis in RAF-Driven murine lung cancer

被引:74
作者
Ceteci, Fatih
Ceteci, Semra
Karreman, Christiaan
Kramer, Boris W.
Asan, Esther
Goetz, Rudolf
Rapp, Ulf R.
机构
[1] Univ Wurzburg, Inst Med Strahlenkunde & Zellforsch, D-97078 Wurzburg, Germany
[2] Univ Kinderklin Wurzuburg, D-97080 Wurzburg, Germany
[3] Univ Wurzburg, Inst Anat & Zellbiol, D-97070 Wurzburg, Germany
关键词
D O I
10.1016/j.ccr.2007.06.014
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Progression of non-small-cell lung cancer (NSCLC) to metastasis is poorly understood. Two genetic approaches were used to evaluate the role of adherens junctions in a C-RAF driven mouse model for NSCLC: conditional ablation of the cdh1 gene and expression of dominant-negative (dn) E-cadherin. Disruption of E-cadherin caused massive formation of intratumoral vessels that was reversible in the early phase of induction. Vascularized tumors grew more rapidly, developed invasive fronts, and gave rise to micrometastasis. beta-catenin was identified as a critical effector of E-cadherin disruption leading to upregulation of VEGF-A and VEGF-C. In vivo, lung tumor cells with disrupted E-cadherin expressed beta-catenin target genes normally found in other endodermal lineages suggesting that reprogramming may be involved in metastatic progression.
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收藏
页码:145 / 159
页数:15
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