Increased invasiveness of osteosarcoma mesenchymal stem cells induced by bone-morphogenetic protein-2 |
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Authors: | Xiao Yang Ya-ping Wang Feng-xiang Liu Ke Zeng Ming-quan Qian Gang Chen Lei Shi Guo-xing Zhu |
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Institution: | 1. Division of Orthopedics, Second People’s hospital of Wuxi, Nanjing Medical University, Wuxi, 214000, People’s Republic of China 2. Division of Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, Shanghai, China
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Abstract: | To evaluate the different traits of mesenchymal stem cell (MSC) isolated from osteosarcoma (OS) and normal bone marrow (BM) induced by bone-morphogenetic protein-2 (BMP-2). MSCs from implanted osteosarcoma or femur bone marrow were isolated and cultured. Differentiation potency was verified and phenotypes were evaluated by flow cytometry. Increased or decreased expressions of BMP-2 were delivered by adenovirus and lentivirus vector, respectively. Expressions of VEGF, EMMPRIN, and MMP-9 were examined. Cell cycle, apoptosis, invasiveness, and proliferation assays were performed between the transfected groups and controls. Increased BMP-2 induced over-expression of VEGF, EMMPRIN, and MMP-9 in OS- and BM-MSCs both intra- and extra-cellularly. Decreased BMP-2 expression induced inhibition of the factors. Increased BMP-2 also induced less population of cells at G1 phase, more apoptotic cells, more cells that invade through Transwell membrane, and faster proliferation in OSMSC compared to those in BMMSC. BMP-2 induced higher expression of tumorigenic factors, which could be responsible for promoting the proliferation and aggressiveness of OSMSC over BMMSC. |
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