title: Heterogeneity of osteosarcoma cell lines led to variable responses in reprogramming.
abstract: Four osteosarcoma cell lines, Saos-2, MG-63, G-292 and U-2 OS, were reprogrammed to pluripotent state using Yamanaka factors retroviral transduction method. Embryonic stem cell (ESC)-like clusters started to appear between 15 to 20 days post transduction. Morphology of the colonies resembled that of ESC colonies with defined border and tightly-packed cells. The reprogrammed sarcomas expressed alkaline phosphatase and pluripotency markers, OCT4, SSEA4, TRA-1-60 and TRA-1-81, as in ESC up to Passage 15. All reprogrammed sarcomas could form embryoid body-like spheres when cultured in suspension in a low attachment dish for up to 10 days. Further testing on the directed differentiation capacity of the reprogrammed sarcomas showed all four reprogrammed sarcoma lines could differentiate into adipocytes while reprogrammed Saos-2-REP, MG-63-REP and G-292-REP could differentiate into osteocytes. Among the 4 osteosarcoma cell lines, U-2 OS reported the highest transduction efficiency but recorded the lowest reprogramming stability under long term culture. Thus, there may be intrinsic differences governing the variable responses of osteosarcoma cell lines towards reprogramming and long term culture effect of the reprogrammed cells. This is a first report to associate intrinsic factors in different osteosarcoma cell lines with variable reprogramming responses and effects on the reprogrammed cells after prolonged culture.
authors.affiliation: 1. MAKNA Cancer Research Institute, Kuala Lumpur, Malaysia; ; 2. Faculty of Medicine and Health Sciences, University Tunku Abdul Rahman (UTAR), Selangor, Malaysia;
authors.forename: Pei Feng
authors.initials: PF
authors.lastname: Choong
authors.affiliation: 2. Faculty of Medicine and Health Sciences, University Tunku Abdul Rahman (UTAR), Selangor, Malaysia;
authors.forename: Hui Xin
authors.initials: HX
authors.lastname: Teh
authors.affiliation: 1. MAKNA Cancer Research Institute, Kuala Lumpur, Malaysia;
authors.forename: Hoon Koon
authors.initials: HK
authors.lastname: Teoh
authors.affiliation: 2. Faculty of Medicine and Health Sciences, University Tunku Abdul Rahman (UTAR), Selangor, Malaysia;
authors.forename: Han Kiat
authors.initials: HK
authors.lastname: Ong
authors.affiliation: 2. Faculty of Medicine and Health Sciences, University Tunku Abdul Rahman (UTAR), Selangor, Malaysia;
authors.forename: Kong Bung
authors.initials: KB
authors.lastname: Choo
authors.affiliation: 3. Fat Metabolism and Stem Cell Group, Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, ASTAR, 138667, Singapore; ; 4. Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore;
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sugii
authors.affiliation: 1. MAKNA Cancer Research Institute, Kuala Lumpur, Malaysia; ; 2. Faculty of Medicine and Health Sciences, University Tunku Abdul Rahman (UTAR), Selangor, Malaysia;
authors.forename: Soon Keng
authors.initials: SK
authors.lastname: Cheong
authors.affiliation: 5. Tissue Engineering Group, National Orthopaedic Centre of Excellence for Research and Learning, Department of Orthopaedic Surgery, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Tunku
authors.initials: T
authors.lastname: Kamarul
mesh_terms: D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D065150:Cellular Reprogramming / Q000235:genetics / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D010011:Osteocytes / Q000166:cytology / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D055746:Stage-Specific Embryonic Antigens / Q000235:genetics / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D011509:Proteoglycans; D055746:Stage-Specific Embryonic Antigens; C107064:TRA-1-60 antigen, human; C519803:TRA-1-81 antigen, human; C066584:stage-specific embryonic antigen-4
keywords: cancer cells; embryonic stem cells; heterogeneity.; osteosarcoma; pluripotency; reprogramming