title: Genomic instability of osteosarcoma cell lines in culture: impact on the prediction of metastasis relevant genes.
abstract: BACKGROUND
  Osteosarcoma is a rare but highly malignant cancer of the bone. As a consequence, the number of established cell lines used for experimental in vitro and in vivo osteosarcoma research is limited and the value of these cell lines relies on their stability during culture. Here we investigated the stability in gene expression by microarray analysis and array genomic hybridization of three low metastatic cell lines and derivatives thereof with increased metastatic potential using cells of different passages.
  
  
  RESULTS
  The osteosarcoma cell lines showed altered gene expression during in vitro culture, and it was more pronounced in two metastatic cell lines compared to the respective parental cells. Chromosomal instability contributed in part to the altered gene expression in SAOS and LM5 cells with low and high metastatic potential. To identify metastasis-relevant genes in a background of passage-dependent altered gene expression, genes involved in "Pathways in cancer" that were consistently regulated under all passage comparisons were evaluated. Genes belonging to "Hedgehog signaling pathway" and "Wnt signaling pathway" were significantly up-regulated, and IHH, WNT10B and TCF7 were found up-regulated in all three metastatic compared to the parental cell lines.
  
  
  CONCLUSIONS
  Considerable instability during culture in terms of gene expression and chromosomal aberrations was observed in osteosarcoma cell lines. The use of cells from different passages and a search for genes consistently regulated in early and late passages allows the analysis of metastasis-relevant genes despite the observed instability in gene expression in osteosarcoma cell lines during culture.
authors.affiliation: Laboratory for Orthopedic Research, Balgrist University Hospital, Zurich, Switzerland.
authors.forename: Roman
authors.initials: R
authors.lastname: Muff
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
authors.forename: Prisni
authors.initials: P
authors.lastname: Rath
authors.affiliation: Laboratory for Orthopedic Research, Balgrist University Hospital, Zurich, Switzerland.
authors.forename: Ram Mohan
authors.initials: RM
authors.lastname: Ram Kumar
authors.affiliation: Laboratory for Orthopedic Research, Balgrist University Hospital, Zurich, Switzerland.
authors.forename: Knut
authors.initials: K
authors.lastname: Husmann
authors.affiliation: Laboratory for Orthopedic Research, Balgrist University Hospital, Zurich, Switzerland.
authors.forename: Walter
authors.initials: W
authors.lastname: Born
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Baudis
authors.affiliation: Laboratory for Orthopedic Research, Balgrist University Hospital, Zurich, Switzerland.
authors.forename: Bruno
authors.initials: B
authors.lastname: Fuchs
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D020869:Gene Expression Profiling; D042822:Genomic Instability; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics / Q000473:pathology*