VDR Status Arbitrates the Prometastatic Effects of Tumor-Associated Macrophages
VDR Status Arbitrates the Prometastatic Effects of Tumor-Associated Macrophages
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VDR 状态决定肿瘤相关巨噬细胞的促转移效应
DOI：
10.1158/1541-7786.mcr-14-0036
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发表时间：
2014-05
影响因子：
5.2
通讯作者：
Tan, Xiaoyue
中科院分区：
文献类型：
--
作者：
Xiong, Min;Wei, Yuquan;Xiang, Rong;Tan, Xiaoyue
肿瘤相关巨噬细胞（TAM）和上皮间质转化（EMT）在转移起始和进展过程中的关系仍不清楚。在此，确定了维生素 D 受体 (VDR) 在转移中的作用，以及 TAM 和 EMT 之间关系的作用。首先，在人类乳腺癌患者或具有差异性转移的乳腺癌小鼠模型的临床组织中检查了VDR的表达水平。这些结果表明，VDR 表达与乳腺癌的转移呈负相关。其次，VDR过度表达的乳腺癌细胞与巨噬细胞系的共培养表明，VDR的过度表达减轻了共培养的巨噬细胞对乳腺癌细胞的促转移作用。此外，VDR 过表达消除了共培养巨噬细胞对乳腺癌细胞 EMT 的诱导，通过 E-钙粘蛋白 (CDH1) 的损失和 α-平滑肌肌动蛋白 (α-SMA) 的诱导来测量。巨噬细胞条件培养基中的TNFα抑制VDR表达，而VDR的下调进一步介导TNFα促进TGFβ诱导的EMT。此外，在 VDR 过表达的乳腺癌细胞和肿瘤异种移植物中，β-连环蛋白的表达受到抑制。最后，给予骨化三醇 [1,25-(OH)2D3]（一种活性维生素 D 代谢物）在体外乳腺癌细胞和小鼠体内乳腺癌模型中发挥类似的抗转移作用，同时保留 VDR 并抑制 β-catenin。意义：TNFα 抑制 VDR 通过增强 β-连环蛋白途径介导 TAM 的促转移作用。摩尔癌症研究中心； 12(8)； 1181–91。 ©2014 AACR。
The relationship between tumor-associated macrophages (TAM) and epithelial-to-mesenchymal transition (EMT) during the initiation and progression of metastasis is still unclear. Here, a role for the vitamin D receptor (VDR) in metastasis was identified, as well as a role in the relationship between TAMs and EMT. First, the expression level of VDR was examined in clinical tissue from human patients with breast cancer or a mouse model of breast cancer with differential metastasis. These results revealed that VDR expression negatively correlates with metastasis in breast cancer. Second, coculture of VDR-overexpressing breast cancer cells with a macrophage cell line demonstrated that overexpression of VDR alleviated the prometastatic effect of cocultured macrophages on breast cancer cells. Furthermore, VDR overexpression abrogated the induction of EMT in breast cancer cells by cocultured macrophage cells, as measured by a loss of E-cadherin (CDH1) and induction of α-smooth muscle actin (α-SMA). TNFα in macrophage conditioned media inhibited VDR expression, whereas downregulation of VDR further mediated the promotion of TGFβ-induced EMT by TNFα. In addition, β-catenin expression was inhibited in VDR-overexpressing breast cancer cells and tumor xenografts. Finally, administration of calcitriol [1,25-(OH)2D3], an active vitamin D metabolite, exerted similar antimetastatic effects in breast cancer cells in vitro and a mouse model of breast cancer in vivo with preservation of VDR and suppression of β-catenin. Implications: VDR suppression by TNFα mediates the prometastatic effect of TAMs through enhancement of the β-catenin pathway. Mol Cancer Res; 12(8); 1181–91. ©2014 AACR.
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影响因子：
7.3
作者：
Mehlen, Patrick
通讯作者：
Mehlen, Patrick
影响因子：
5.9
作者：
Moukayed M;Grant WB
通讯作者：
Grant WB
DOI：
--
发表时间：
2007
期刊：
American journal of physiology. Regulatory, integrative and comparative physiology
影响因子：
--
作者：
K. Meldrum;R. Misseri;P. Metcalfe;C. Dinarello;K. Hile;D. Meldrum
通讯作者：
K. Meldrum;R. Misseri;P. Metcalfe;C. Dinarello;K. Hile;D. Meldrum
DOI：
10.1016/s0140-6736(54)91627-x
发表时间：
2004
期刊：
--
影响因子：
--
作者：
V. B. Lorca;Yuxi Zhou;Charlotte Yang;Silvana Duran;Colin Kruse;Prateek Kulkarni;Todd McHugh;Joseph Terry;Elizabeth Jensen;Delaney K. Geitgey;Maria Onusko;J. Kuhn;S. McKenna;Julie Slyby;Emily Davis;Yanyang Cao;Pratik Shriwas;A. Hearne;Maria Onsuko;Ebi PI's;Nih Grant Funding;Hannah Walker;Shiyong Wu;Hao Chen;Xiaozhuo Chen;Venki Ramakrishnan
通讯作者：
V. B. Lorca;Yuxi Zhou;Charlotte Yang;Silvana Duran;Colin Kruse;Prateek Kulkarni;Todd McHugh;Joseph Terry;Elizabeth Jensen;Delaney K. Geitgey;Maria Onusko;J. Kuhn;S. McKenna;Julie Slyby;Emily Davis;Yanyang Cao;Pratik Shriwas;A. Hearne;Maria Onsuko;Ebi PI's;Nih Grant Funding;Hannah Walker;Shiyong Wu;Hao Chen;Xiaozhuo Chen;Venki Ramakrishnan
影响因子：
3.7
作者：
Stuelten CH;Cervoni-Curet FN;Busch JI;Sutton E;Webster JD;Kavalukas SL;Wakefield LM;Barbul A;Niederhuber JE
通讯作者：
Niederhuber JE