The evolution of endothelial regulatory paradigms in cancer biology and vascular repair.
The evolution of endothelial regulatory paradigms in cancer biology and vascular repair.
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DOI：
10.1158/0008-5472.can-11-1718
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发表时间：
2011-12-15
期刊：
影响因子：
11.2
通讯作者：
Edelman ER
中科院分区：
文献类型：
--
作者：
Franses JW;Edelman ER
虽然内皮细胞在癌症中的作用主要被认为与肿瘤灌注有关，但对“血管分泌”调节的新认识将基质调节能力添加到肿瘤中内皮功能的扩展列表中。我们认为，了解在血管疾病和修复中建立的状态依赖性旁分泌调节模式对于深入了解肿瘤生物学至关重要，因为内皮细胞调节所有血管化组织中的不同过程。我们现在概述的历史发展，导致赞赏的旁分泌调节功能的内皮细胞，总结血管和基质在癌症中的经典观点，并试图合并这些想法，包括基质调节内皮细胞作为一个关键的调节癌症。内皮细胞作为癌症状态的生物化学调节剂与其肿瘤处于恒定的动态平衡的概念可能影响癌症的诊断、预后和治疗。这些概念可能很好地解释了抗血管生成癌症疗法的混合结果，以及某些改善血管健康的药物如何与改善癌症预后相关。
Although the roles of endothelial cells in cancer have been primarily considered to be related to tumor perfusion, the emerging appreciation of “angiocrine” regulation adds stromal regulatory capabilities to the expanding list of endothelial functions in tumors. We posit that understanding the state-dependent paracrine regulatory paradigms established in vascular disease and repair will be critical for a deep understanding of tumor biology, as endothelial cells regulate diverse processes in all vascularized tissues. We now outline the historical developments that led to the appreciation of the paracrine regulatory functions of endothelial cells, summarize classical views of blood vessels and stroma in cancer, and attempt to merge these ideas to include the stromal regulatory endothelial cell as a critical regulator of cancer. The notion of the endothelial cell as a biochemical regulator of cancer state in constant dynamic balance with its tumor could impact diagnosis, prognosis and treatment of cancer. Such concepts might well explain the mixed results from anti-angiogenic cancer therapeutics and how certain drugs that improve vascular health correlate with improved cancer prognosis.