title: Cisplatin promotes mesenchymal-like characteristics in osteosarcoma through Snail.
abstract: More than 30% of patients with osteosarcoma succumb to pulmonary metastases. Epithelial-mesenchymal transition (EMT) is a biological process by which tumor cells gain an increased capacity for invasiveness and metastasis. A previous study confirmed the phenomenon of EMT in osteosarcoma, a mesenchymal-derived tumor. However, whether chemotherapy affects EMT remains to be elucidated. In the present study, the osteosarcoma cells were exposed to a sublethal dose of cisplatin, and any surviving cells were assumed to be more resistant to cisplatin. In addition, these cells exhibited a more mesenchymal phenotype. Immunofluorescence analysis revealed that the cisplatin treated cells had an increased long/short axis ratio and increased expression of N-cadherin compared with control cells. A panel of EMT-associated genes was subsequently assessed by quantitative PCR and western blot analysis, and they were observed to be significantly upregulated in the cisplatin treated cells. Thein vitrowound healing and Transwell assay indicated that the cisplatin treated cells were more prone to migrate and invade. Anin vivoassay showed that the cisplatin-treated xenograft had increased expression of EMT-associated genes, and exhibited increased pulmonary lesions compared with the control, which indicated an elevated capacity to metastasize. The expression of Snail was knocked down by specific small interfering RNA, and it was observed that Snail inhibition promoted cisplatin sensitivity, and cisplatin-induced EMT was significantly blocked. Taken together, the results of the present study supported that idea that Snail participates in cisplatin-induced EMT in osteosarcoma cells, and targeting EMT-transcription factors may offer promise for the therapeutics of osteosarcoma.
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Fang
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Orthopedics, Wuhan No. 5 Hospital, Wuhan, Hubei 430050, P.R. China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Mei
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Orthopedic Oncology, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital and Institute, Beijing 100871, P.R. China.
authors.forename: Tian
authors.initials: T
authors.lastname: Gao
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Anyuan
authors.initials: A
authors.lastname: Cheng
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Weichun
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Kezhou
authors.initials: K
authors.lastname: Xia
authors.affiliation: Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Gaiwei
authors.initials: G
authors.lastname: Liu
keywords: cisplatin; epithelial-mesenchymal transition; osteosarcoma; snail; targeted therapy