Anti-proliferative effects of calcitriol on endothelial cells derived from two different microenvironments
Anti-proliferative effects of calcitriol on endothelial cells derived from two different microenvironments
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DOI：
10.1016/j.jsbmb.2006.12.042
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发表时间：
2007-03-01
影响因子：
4.1
通讯作者：
Trump, Donald L.
中科院分区：
文献类型：
--
作者：
Chung, Ivy;Yu, Wei-Dong;Trump, Donald L.
骨化三醇（1，25-二羟基胆钙化醇），维生素D的活性形式，在肿瘤细胞和肿瘤衍生的内皮细胞（TDEC）中具有抗增殖作用。然而，从正常组织中分离的内皮细胞（细胞系）或新鲜分离的细胞或从植入的基质胶塞（MDEC）中分离的内皮细胞相对具有抵抗力。TDEC和。MDEC表达相似量的维生素D受体（VDR）蛋白。虽然来自TDEC的VDR比来自MDEC的VDR对骨化三醇具有更高的结合亲和力，但两种细胞类型中的VDR都易位到细胞核并反式激活24-羟化酶启动子-荧光素酶构建体。骨化三醇通过诱导G（0）/G（1）细胞周期阻滞和促进细胞凋亡选择性抑制TDEC而非MDEC的生长。这种选择性似乎与24-羟化酶（CYP 24）表达有关。骨化三醇显著诱导MDEC中的CYP 24表达，但不诱导TDEC中的CYP 24表达，并且MDEC中的CYP 24活性抑制恢复了它们对骨化三醇的敏感性。这些发现表明，从不同微环境（TDEC与MDEC）中分离的内皮细胞中CYP 24表达的诱导不同，这种差异有助于这些细胞类型中选择性骨化三醇介导的生长抑制。(c)2006爱思唯尔有限公司版权所有。
Calcitriol (1,25-dihydroxycholecalciferol), the active form of Vitamin D, is anti-proliferative in tumor cells and tumor-derived endothelial cells (TDEC). However, endothelial cells isolated from normal tissues as cell lines or freshly isolated cells or from implanted Matrigel plugs (MDEC) are relatively resistant. Both TDEC and. MDEC express similar amounts of Vitamin D receptor (VDR) protein. Although the VDR from TDEC has higher binding affinity for calcitriol than those from MDEC, VDR in both cell types translocates to the nucleus and transactivates the 24-hydroxylase promoter-luciferase construct. Calcitriol selectively inhibits the growth of TDEC but not MDEC by inducing G(0)/G(1) cell cycle arrest and by promoting apoptosis. This selectivity appears to be related to 24-hydroxylase (CYP24) expression. Calcitriol significantly induced CYP24 expression in MDEC but not in TDEC and inhibition of CYP24 activity in MDEC restores their sensitivity to calcitriol. These findings indicate that the induction of CYP24 expression differs in endothelial cells isolated from different microenvironments (TDEC versus MDEC) and that this distinction contributes to selective calcitriol-mediated growth inhibition in these cell types. (c) 2006 Elsevier Ltd. All rights reserved.