Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Oncogene. 2012 Apr 5;31(14):1757-70. doi: 10.1038/onc.2011.365. Epub 2011 Aug 22.
Most cases of breast cancer (BrCa) mortality are due to vascular metastasis. BrCa cells must intravasate through endothelial cells (ECs) to enter a blood vessel in the primary tumor and then adhere to ECs and extravasate at the metastatic site. In this study we demonstrate that inhibition of hypoxia-inducible factor (HIF) activity in BrCa cells by RNA interference or digoxin treatment inhibits primary tumor growth and also inhibits the metastasis of BrCa cells to the lungs by blocking the expression of angiopoietin-like 4 (ANGPTL4) and L1 cell adhesion molecule (L1CAM). ANGPTL4 is a secreted factor that inhibits EC-EC interaction, whereas L1CAM increases the adherence of BrCa cells to ECs. Interference with HIF, ANGPTL4 or L1CAM expression inhibits vascular metastasis of BrCa cells to the lungs.
大多数乳腺癌（BrCa）死亡病例是由于血管转移。BrCa 细胞必须穿过内皮细胞（ECs）才能进入原发性肿瘤中的血管，然后在转移部位黏附并穿出 ECs。在这项研究中，我们证明通过 RNA 干扰或地高辛处理抑制 BrCa 细胞中的缺氧诱导因子（HIF）活性，可通过阻断血管生成素样 4（ANGPTL4）和 L1 细胞黏附分子（L1CAM）的表达来抑制原发性肿瘤生长，并抑制 BrCa 细胞向肺部的转移。ANGPTL4 是一种分泌因子，可抑制 EC-EC 相互作用，而 L1CAM 则增加 BrCa 细胞与 ECs 的黏附。干扰 HIF、ANGPTL4 或 L1CAM 的表达可抑制 BrCa 细胞向肺部的血管转移。
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