Suppression of epithelial ovarian cancer invasion into the omentum by 1α,25-dihydroxyvitamin D3 and its receptor.
Suppression of epithelial ovarian cancer invasion into the omentum by 1α,25-dihydroxyvitamin D3 and its receptor.
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DOI：
10.1016/j.jsbmb.2014.11.005
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发表时间：
2015-04
影响因子：
4.1
通讯作者：
Bai, Wenlong
中科院分区：
文献类型：
--
作者：
Lungchukiet, Panida;Sun, Yuefeng;Kasiappan, Ravi;Quarni, Waise;Nicosia, Santo V.;Zhang, Xiaohong;Bai, Wenlong
上皮性卵巢癌（EOC）是女性妇科癌症死亡的主要原因，主要是因为它在诊断时已经扩散到腹膜腔中的网膜等腹膜内组织。本研究通过体外实验、离体网膜器官培养系统和野生型（WT）和维生素D受体（VDR）基因敲除小鼠的肿瘤模型，探讨1α，25-二羟维生素D3（1，25 D3）和VDR对卵巢上皮癌侵袭的影响。用1，25 D3处理人EOC细胞在单层划痕和transwell测定中抑制了它们的迁移和侵袭，并且抑制了它们在离体系统中定殖网膜的能力，支持上皮VDR在干扰EOC侵袭中的作用。此外，在不存在1，25 D3的情况下，OVCAR 3细胞中的VDR敲低增加了它们在离体系统中定殖网膜的能力，显示了上皮VDR对EOC侵袭的潜在配体非依赖性抑制。在同系模型中，ID 8肿瘤表现出比WT小鼠更强的定殖VDR缺失的网膜的能力;用EB 1089预处理WT而不是VDR缺失的小鼠减少了ID 8定殖，揭示了基质VDR在抑制EOC侵袭中的作用。这些研究首次证明了上皮和基质VDR在介导1，25 D3活性中的作用以及VDR在抑制EOC侵袭中的1，25 D3独立作用。这些数据表明，基于VDR的药物发现可能会导致新的干预策略的发展，以提高晚期EOC患者的生存率。本文是题为“维生素D研讨会”的特刊的一部分。
Epithelial ovarian cancer (EOC) is the leading cause of gynecological cancer death in women, mainly because it has spread to intraperitoneal tissues such as the omentum in the peritoneal cavity by the time of diagnosis. In the present study, we established in vitro assays, ex vivo omental organ culture system and syngeneic animal tumor models using wild type (WT) and vitamin D receptor (VDR) null mice to investigate the effects of 1α,25-dihydroxyvitamin D3 (1,25D3) and VDR on EOC invasion. Treatment of human EOC cells with 1,25D3 suppressed their migration and invasion in monolayer scratch and transwell assays and ability to colonize the omentum in the ex vivo system, supporting a role for epithelial VDR in interfering with EOC invasion. Furthermore, VDR knockdown in OVCAR3 cells increased their ability to colonize the omentum in the ex vivo system in the absence of 1,25D3, showing a potential ligand-independent suppression of EOC invasion by epithelial VDR. In syngeneic models, ID8 tumors exhibited an increased ability to colonize omenta of VDR null over that of WT mice; pre-treatment of WT, not VDR null, mice with EB1089 reduced ID8 colonization, revealing a role for stromal VDR in suppressing EOC invasion. These studies are the first to demonstrate a role for epithelial and stromal VDR in mediating the activity of 1,25D3 as well as a 1,25D3-independent action of the VDR in suppressing EOC invasion. The data suggest that VDR-based drug discovery may lead to the development of new intervention strategies to improve the survival of patients with EOC at advanced stages. This article is part of a Special Issue entitled “Vitamin D Workshop”.
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DOI：
10.1016/j.jsbmb.2012.09.021
发表时间：
2013-07
影响因子：
4.1
作者：
Bikle, Daniel D.;Elalieh, Hashem;Welsh, JoEllen;Oh, Dennis;Cleaver, James;Teichert, Arnaud
通讯作者：
Teichert, Arnaud
影响因子：
6
作者：
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Rinker-Schaeffert, Carrie
影响因子：
4
作者：
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通讯作者：
Welsh J
影响因子：
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作者：
Kenny, Hilary A.;Dogan, Songuel;Zillhardt, Marion;Mitra, Anirban K.;Yamada, S. Diane;Krausz, Thomas;Lengyel, Ernst
通讯作者：
Lengyel, Ernst
影响因子：
4.8
作者：
Li, YC;Pirro, AE;Demay, MB
通讯作者：
Demay, MB