Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292.
Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292.
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DOI：
10.1007/s10585-011-9398-4
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发表时间：
2011-10
影响因子：
4
通讯作者：
Mori, Kazushige
中科院分区：
文献类型：
--
作者：
Furugaki, Koh;Moriya, Yoichiro;Iwai, Toshiki;Yorozu, Keigo;Yanagisawa, Mieko;Kondoh, Kumiko;Fujimoto-Ohuchi, Kaori;Mori, Kazushige
关键词：
以往的临床前和临床研究结果表明，表皮生长因子受体（EGFR）在破骨细胞分化和肿瘤骨转移的发病机制中的潜在作用。在这项研究中，我们研究了厄洛替尼，一种口服活性EGFR酪氨酸激酶抑制剂（TKI），对人非小细胞肺癌（NSCLC）细胞系NCI-H292骨侵袭的影响。首先，我们建立了一种新的NCI-H292细胞溶骨性骨侵袭模型，该模型是通过将NCI-H292细胞植入scid小鼠胫骨中来建立的。在该模型中，NCI-H292细胞显著激活胫骨中的破骨细胞，这导致溶骨性骨破坏。厄洛替尼治疗通过抑制骨转移部位成骨细胞/基质细胞中NF-κB配体受体激活因子（RANKL）的表达，将破骨细胞活化抑制至基础水平，从而抑制NCI-H292细胞引起的溶骨性骨破坏。厄洛替尼在体外对NCI-H292细胞增殖有抑制作用。厄洛替尼抑制NCI-H292细胞中溶骨性因子的产生，如甲状旁腺相关蛋白（PTHrP）、IL-8、IL-11和血管内皮生长因子（VEGF）。此外，厄洛替尼还抑制体外成骨细胞/基质细胞增殖和RANKL诱导的体外破骨细胞发育。总之，厄洛替尼通过抑制骨转移部位的肿瘤生长、肿瘤细胞中溶骨因子的产生、成骨细胞/基质细胞增殖和小鼠骨髓细胞的破骨细胞分化来抑制破骨细胞活化，从而抑制骨转移中肿瘤诱导的溶骨侵袭。
Previous preclinical and clinical findings have suggested a potential role of epidermal growth factor receptor (EGFR) in osteoclast differentiation and the pathogenesis of bone metastasis in cancer. In this study, we investigated the effect of erlotinib, an orally active EGFR tyrosine kinase inhibitor (TKI), on the bone invasion of human non-small-cell lung cancer (NSCLC) cell line NCI-H292. First, we established a novel osteolytic bone invasion model of NCI-H292 cells which was made by inoculating cancer cells into the tibia of scid mice. In this model, NCI-H292 cells markedly activated osteoclasts in tibia, which resulted in osteolytic bone destruction. Erlotinib treatment suppressed osteoclast activation to the basal level through suppressing receptor activator of NF-κB ligand (RANKL) expression in osteoblast/stromal cell at the bone metastatic sites, which leads to inhibition of osteolytic bone destruction caused by NCI-H292 cells. Erlotinib inhibited the proliferation of NCI-H292 cells in in vitro. Erlotinib suppressed the production of osteolytic factors, such as parathyroid hormone-related protein (PTHrP), IL-8, IL-11 and vascular endothelial growth factor (VEGF) in NCI-H292 cells. Furthermore, erlotinib also inhibited osteoblast/stromal cell proliferation in vitro and the development of osteoclasts induced by RANKL in vitro. In conclusion, erlotinib inhibits tumor-induced osteolytic invasion in bone metastasis by suppressing osteoclast activation through inhibiting tumor growth at the bone metastatic sites, osteolytic factor production in tumor cells, osteoblast/stromal cell proliferation and osteoclast differentiation from mouse bone marrow cells.
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影响因子：
4.6
作者：
Quint, LE;Tummala, S;Orringer, MB
通讯作者：
Orringer, MB
影响因子：
3.9
作者：
Angelucci, A;Gravina, GL;Bologna, M
通讯作者：
Bologna, M
影响因子：
3.9
作者：
Normanno, N;De Luca, A;Pinto, A
通讯作者：
Pinto, A
影响因子：
7.3
作者：
Kitazawa, S;Kitazawa, R
通讯作者：
Kitazawa, R
影响因子：
8.8
作者：
Lorch, G.;Gilmore, J. L.;Koltz, P. F.;Gonterman, R. M.;Laughner, R.;Lewis, D. A.;Konger, R. L.;Nadella, K. S.;Toribio, R. E.;Rosol, T. J.;Foley, J.
通讯作者：
Foley, J.