LYVE-1 is not restricted to the lymph vessels: expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis.
LYVE-1 is not restricted to the lymph vessels: expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis.
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发表时间：
2001-11
期刊：
影响因子：
11.2
通讯作者：
C. M. Carreira;S. Nasser;E. Tomaso;T. Padera;Y. Boucher;S. Tomarev;R. Jain
中科院分区：
文献类型：
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作者：
C. M. Carreira;S. Nasser;E. Tomaso;T. Padera;Y. Boucher;S. Tomarev;R. Jain
淋巴管内皮细胞透明质酸受体(LYVE)-1被认为仅限于淋巴管，已被用来表明肿瘤淋巴管的生成是通过淋巴管生成因子在小鼠肿瘤模型中过度表达而发生的。然而，这些研究尚未在人类肿瘤中得到证实。在这里，我们首先表明，LYVE-1并不是淋巴管所特有的。事实上，LYVE-1也存在于小鼠和人类的正常肝血窦内皮细胞中。令人惊讶的是，LYVE-1在人肝肿瘤的血管新生血管中缺失，仅在肝硬变的再生肝结节的微循环中微弱存在，尽管这两种血管主要来自肝窦。其次，我们提出了一种新的方法来识别人和小鼠肝脏中的淋巴管。结合Lyve-1和Prox1(一种转录因子)免疫组织化学，我们证明了在肝硬变中淋巴管丰富。相比之下，在人肝细胞癌和肝转移瘤中，它们仅限于肿瘤边缘和周围肝脏。肝细胞癌和肝转移瘤中肿瘤内淋巴管的缺失可能会损害这些肿瘤的分子和细胞转运。最后，LYVE-1在肝窦内皮细胞中的存在表明LYVE-1具有超越淋巴血管系统的功能。
Lymphatic vessel endothelial hyaluronan receptor (LYVE)-1 is thought to be restricted to lymph vessels and has been used as such to show that tumor lymphangiogenesis occurs on overexpression of lymphangiogenic factors in mouse tumor models. However, these studies have not yet been corroborated in human tumors. Here we show, first, that LYVE-1 is not exclusive to the lymph vessels. Indeed, LYVE-1 is also present in normal hepatic blood sinusoidal endothelial cells in mice and humans. Surprisingly, LYVE-1 is absent from the angiogenic blood vessels of human liver tumors and only weakly present in the microcirculation of regenerative hepatic nodules in cirrhosis, though both vessels are largely derived from the liver sinusoids. Second, we propose a novel approach to identify lymphatics in human and murine liver. By combining LYVE-1 and Prox 1 (a transcription factor) immunohistochemistry, we demonstrate that lymphatics are abundant in cirrhosis. In contrast, in human hepatocellular carcinoma and liver metastases, they are restricted to the tumor margin and surrounding liver. The absence of intratumor lymphatics in hepatocellular carcinomas and liver metastases may impair molecular and cellular transport in these tumors. Finally, the presence of LYVE-1 in liver sinusoidal endothelia suggests that LYVE-1 has functions beyond the lymph vascular system.