title: Increased invasiveness of osteosarcoma mesenchymal stem cells induced by bone-morphogenetic protein-2.
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.
authors.affiliation: Division of Orthopedics, Second People's hospital of Wuxi, Nanjing Medical University, Wuxi 214000, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.forename: Ya-ping
authors.initials: YP
authors.lastname: Wang
authors.forename: Feng-xiang
authors.initials: FX
authors.lastname: Liu
authors.forename: Ke
authors.initials: K
authors.lastname: Zeng
authors.forename: Ming-quan
authors.initials: MQ
authors.lastname: Qian
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Guo-xing
authors.initials: GX
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism*; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005434:Flow Cytometry; D005822:Genetic Vectors; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D014162:Transfection
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2