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In vivo selection for spine-derived highly metastatic lung cancer cells is associated with increased migration, inflammation and decreased adhesion
Oncotarget Pub Date : 2015-06-10 , DOI: 10.18632/oncotarget.4416
Xiaopan Cai 1 , Jian Luo 2 , Xinghai Yang 1 , Huayun Deng 2 , Jishen Zhang 1 , Shichang Li 3 , Haifeng Wei 1 , Cheng Yang 1 , Leqin Xu 1 , Rongrong Jin 2 , Zhenxi Li 1 , Wang Zhou 1 , JianDong Ding 1 , Jianjun Chu 4 , Lianshun Jia 1 , Qi Jia 1 , Chengjun Tan 5 , Mingyao Liu 1, 6 , Jianru Xiao 1
Affiliation  

We developed a murine spine metastasis model by screening five metastatic non-small cell lung cancer cell lines (PC-9, A549, NCI-H1299, NCI-H460, H2030). A549 cells displayed the highest tendency towards spine metastases. After three rounds of selection in vivo, we isolated a clone named A549L6, which induced spine metastasis in 80% of injected mice. The parameters of the A549L6 cell spinal metastatic mouse models were consistent with clinical spine metastasis features. All the spinal metastatic mice developed symptoms of nerve compression after 40 days. A549L6 cells had increased migration, invasiveness and decreased adhesion compared to the original A549L0 cells. In contrast, there was no significant differences in cell proliferation, apoptosis and sensitivity to chemotherapeutic agents such as cisplatin. Comparative transcriptomic analysis and Real-time PCR analysis showed that expression of signaling molecules regulating several tumor properties including migration (MYL9), metastasis (CEACAM6, VEGFC, CX3CL1, CST1, CCL5, S100A9, IGF1, NOTCH3), adhesion (FN1, CEACAM1) and inflammation (TRAF2, NFκB2 and RelB) were altered in A549L6 cells. We suggest that migration, adhesion and inflammation related genes contribute to spine metastatic capacity.

中文翻译:

脊柱来源的高转移性肺癌细胞的体内选择与迁移,炎症和粘附减少有关

我们通过筛选五种转移性非小细胞肺癌细胞系(PC-9,A549,NCI-H1299,NCI-H460,H2030)建立了小鼠脊柱转移模型。A549细胞显示出最高的脊柱转移趋势。经过三轮体内选择,我们分离出一个名为A549L6的克隆,该克隆在80%的注射小鼠中诱导了脊柱转移。A549L6细胞脊柱转移小鼠模型的参数与临床脊柱转移特征一致。40天后,所有脊髓转移小鼠均出现神经受压症状。与原始A549L0细胞相比,A549L6细胞具有增加的迁移,侵袭性和降低的粘附性。相反,在细胞增殖,凋亡和对化学治疗剂如顺铂的敏感性方面没有显着差异。对比转录组学分析和实时PCR分析表明,信号分子的表达调节多种肿瘤特性,包括迁移(MYL9),转移(CEACAM6,VEGFC,CX3CL1,CST1,CCL5,S100A9,IGF1,NOTCH3),粘附(FN1,CEACAM1)和炎症(TRAF2,NFκB2和RelB)在A549L6细胞中发生了改变。我们建议迁移,粘附和炎症相关基因有助于脊柱转移能力。
更新日期:2015-06-10
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