title: In vivo selection for spine-derived highly metastatic lung cancer cells is associated with increased migration, inflammation and decreased adhesion.
abstract: 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.
authors.affiliation: 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.
authors.forename: Xiaopan
authors.initials: X
authors.lastname: Cai
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Luo
authors.affiliation: 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.
authors.forename: Xinghai
authors.initials: X
authors.lastname: Yang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, P.R. China.
authors.forename: Huayun
authors.initials: H
authors.lastname: Deng
authors.affiliation: 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.
authors.forename: Jishen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai, P.R. China.
authors.forename: Shichang
authors.initials: S
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wei
authors.affiliation: 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.
authors.forename: Cheng
authors.initials: C
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Leqin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, P.R. China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Jin
authors.affiliation: 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.
authors.forename: Zhenxi
authors.initials: Z
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Wang
authors.initials: W
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: JianDong
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Orthopedics, Binhu Hospital, The First People's Hospital of Hefei City, Hefei, P.R. China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Chu
authors.affiliation: 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.
authors.forename: Lianshun
authors.initials: L
authors.lastname: Jia
authors.affiliation: 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.
authors.forename: Qi
authors.initials: Q
authors.lastname: Jia
authors.affiliation: Department of General Surgery, The Fifth People's Hospital of Qinghai Province, Qinghai, P.R. China.
authors.forename: Chengjun
authors.initials: C
authors.lastname: Tan
authors.affiliation: 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.|Center for Cancer and Stem Cell Biology, Alkek Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX, USA.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Jianru
authors.initials: J
authors.lastname: Xiao
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude
keywords: A549; bone metastasis; lung cancer; spine metastasis