In vivo selection for spine-derived highly metastatic lung cancer cells is associated with increased migration, inflammation and decreased adhesion

被引:27
作者
Cai, Xiaopan [1 ,2 ]
Luo, Jian [3 ,4 ]
Yang, Xinghai [1 ,2 ]
Deng, Huayun [3 ,4 ]
Zhang, Jishen [1 ,2 ]
Li, Shichang [5 ]
Wei, Haifeng [1 ,2 ]
Yang, Cheng [1 ,2 ]
Xu, Leqin [1 ,2 ]
Jin, Rongrong [3 ,4 ]
Li, Zhenxi [1 ,2 ]
Zhou, Wang [1 ,2 ]
Ding, JianDong [1 ,2 ]
Chu, Jianjun [6 ]
Jia, Lianshun [1 ,2 ]
Jia, Qi [1 ,2 ]
Tan, Chengjun [7 ]
Liu, Mingyao [1 ,2 ,8 ]
Xiao, Jianru [1 ,2 ]
机构
[1] E China Normal Univ, Shanghai 200062, Peoples R China
[2] Second Mil Med Univ, Shanghai Changzheng Hosp, Joint Res Ctr Orthoped Oncol, Dept Orthoped Oncol,Changzheng Hosp, Shanghai, Peoples R China
[3] E China Normal Univ, Shanghai Key Lab Regulatory Biol, Inst Biomed Sci, Shanghai 200062, Peoples R China
[4] E China Normal Univ, Sch Life Sci, Shanghai 200062, Peoples R China
[5] E China Normal Univ, Key Lab Adolescent Hlth Assessment & Exercise Int, Minist Educ, Shanghai 200062, Peoples R China
[6] First Peoples Hosp Hefei City, Binhu Hosp, Dept Orthoped, Hefei, Peoples R China
[7] Fifth Peoples Hosp Qinghai Prov, Dept Gen Surg, Shanghai, Qinghai, Peoples R China
[8] Texas A&M Univ, Hlth Sci Ctr, Ctr Canc & Stem Cell Biol, Alkek Inst Biosci & Technol, Houston, TX USA
基金
中国国家自然科学基金;
关键词
lung cancer; bone metastasis; spine metastasis; A549; NF-KAPPA-B; RECURRENCE-FREE SURVIVAL; BONE METASTASIS; PROGRESSION; EXPRESSION; OSTEOCLASTOGENESIS; FIBRONECTIN; RESISTANCE; TUMORS; MODEL;
D O I
10.18632/oncotarget.4416
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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, NF.B2 and RelB) were altered in A549L6 cells. We suggest that migration, adhesion and inflammation related genes contribute to spine metastatic capacity.
引用
收藏
页码:22905 / 22917
页数:13
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