Meng Fanyin, Henson Roger, Patel Tushar
Dept of Internal Medicine, The Ohio State University, 514A Tzagournis Medical Research Facility, Columbus, OH 43210, USA.
Am J Physiol Cell Physiol. 2007 Aug;293(2):C749-60. doi: 10.1152/ajpcell.00537.2006. Epub 2007 May 30.
Targeting endothelial cells (EC) that line tumor blood vessels forms the basis for metronomic therapy and is a promising new strategy for the treatment of cancer. Genetic and phenotypic differences between tumor-derived and normal ECs indicate that targeting tumor ECs may be therapeutically useful. In the present study, we examined differences in responses to chemotherapy in microvascular EC lines from tumoral (T-EC) and normal (N-EC) mouse liver tissues. The identity of these cells was confirmed by immunocytochemistry for EC markers, such as vascular endothelial-cadherin and CD31 for both types of ECs, and the tumor-endothelial-specific marker tumor endothelial marker-7 for T-EC. The involvement of Akt in NF-kappaB-dependent angiogenesis was different between N-EC and T-EC. Chemotherapeutic stress increased angiogenesis in T-EC, but not N-EC via an NF-kappaB-Akt-dependent manner. Both NF-kappaB and Akt were involved in enhanced survival and migration in T-EC in response to chemotherapeutic stress. Moreover, Akt was involved in NF-kappaB-dependent VEGF expression and angiogenesis. These studies, showing differences in cellular responses to chemotherapy in tumor-derived ECs, indicate that specific therapies targeting these cells may be therapeutically useful for liver cancers.
靶向肿瘤血管内衬的内皮细胞（EC）是节拍疗法的基础，也是一种有前景的癌症治疗新策略。肿瘤来源的内皮细胞与正常内皮细胞之间的基因和表型差异表明，靶向肿瘤内皮细胞可能具有治疗作用。在本研究中，我们检测了来自肿瘤（T-EC）和正常（N-EC）小鼠肝脏组织的微血管内皮细胞系对化疗反应的差异。通过免疫细胞化学检测两种内皮细胞的内皮细胞标志物（如血管内皮钙黏蛋白和CD31）以及T-EC的肿瘤内皮特异性标志物肿瘤内皮标志物-7，确认了这些细胞的身份。N-EC和T-EC中Akt参与NF-κB依赖性血管生成的情况有所不同。化疗应激通过NF-κB-Akt依赖性方式增加T-EC中的血管生成，但不增加N-EC中的血管生成。NF-κB和Akt均参与T-EC对化疗应激的存活和迁移增强。此外，Akt参与NF-κB依赖性VEGF表达和血管生成。这些研究表明肿瘤来源的内皮细胞对化疗的细胞反应存在差异，提示针对这些细胞的特异性疗法可能对肝癌具有治疗作用。
