In vivo selection for spine-derived highly metastatic lung cancer cells is associated with increased migration, inflammation and decreased adhesion
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Xiaopan Cai1,*, Jian Luo2,*,**, Xinghai Yang1,*, Huayun Deng2, Jishen Zhang1, Shichang Li3, Haifeng Wei1, Cheng Yang1, Leqin Xu1, Rongrong Jin2, Zhenxi Li1, Wang Zhou1, JianDong Ding1, Jianjun Chu4, Lianshun Jia1, Qi Jia1, Chengjun Tan5, Mingyao Liu1,6,** and Jianru Xiao1,**
1 East China Normal University and Shanghai Changzheng Hospital Joint Research Center for Orthopedic Oncology, Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai, P. R. China
2 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, P. R. China
3 The Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai, P. R. China
4 Department of Orthopedics, Binhu Hospital, The First People’s Hospital of Hefei City, Hefei, P. R. China
5 Department of General Surgery, The Fifth People’s Hospital of Qinghai Province, Qinghai, P. R. China
6 Center for Cancer and Stem Cell Biology, Alkek Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX, USA
* These authors have contributed equally to this work
** These authors are co-senior authors
Jian Luo, email:
Mingyao Liu, email:
Jianru Xiao, email:
Keywords: lung cancer; bone metastasis; spine metastasis; A549
Received: February 02, 2015 Accepted: May 29, 2015 Published: June 10, 2015
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.
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