title: The novel myxofibrosarcoma cell line MUG-Myx1 expresses a tumourigenic stem-like cell population with high aldehyde dehydrogenase 1 activity.
abstract: BACKGROUND
  Myxofibrosarcoma comprises a spectrum of malignant neoplasms withprominent myxoid stromata, cellular pleomorphism, and distinct curvilinear vascular patterns. These neoplasms mainly affect patients in the sixth to eighth decades of life and the overall 5-year survival rate is 60-70%.
  
  
  METHODS
  After the establishment of the novel myxofibrosarcoma cell lines MUG-Myx1, cells were characterized using short tandem repeat (STR), copy number variation (CNV), and genotype/loss-of-heterozygosity (LOH) analyses. The growth behaviour of the cells was analyzed with the xCELLigence system and an MTS assay. The tumourigenicity of MUG-Myx1 was proved in NOD/SCID mice. Additionally, a stem-like cell population with high enzymatic activity of aldehyde dehydrogenase 1 (ALDH1(high)) was isolated for the first time from myxofibrosarcoma cells using the Aldefluor® assay followed by FACS analysis.
  
  
  RESULTS
  The frozen primary parental tumour tissue and the MUG-Myx1 cell line showed the same STR profile at the markers D3S1358, TH01, D21S11, D18S51, Penta E, D5S818, D13S317, D7S820, D16S539, CSF1PO, Penta D, Amelogenin, D8S1179, TPOX, and FGY. Typically, myxofibrosarcoma gain and/or amplification was mapped to 7p21.3-q31.1, q31.1-q31.33, q33-q36.2, p21.3, p21.2, p14.1-q11.23, q31.33-q33, p21.2-p14.1, q11.23-q21.3, q36.2-q36.3, which, respectively are known to harbour tumour-associated genes, including TIF, BRAF, MLL3, SMO, and MET. Typically an LOH for myxofibrosarcoma on chr5 q21 was found. In addition, MUG-Myx1 ALDH1(high) cells showed an upregulation of the ABC transporter ABCB1 and ABCG2; higher c-Myc, E-cadherin and SOX-2 expression; and a higher potential for tumourigenicity and proliferation levels.
  
  
  CONCLUSIONS
  The new myxofibrosarcoma cell line MUG-Myx1 was established to enrich the bank of publicly available cell lines, with respect to providing comprehensive genetic and epigenetic characterization. Furthermore, because of their tumourigenicity, the cell line is also suitable for in vivo experiments.
authors.affiliation: Department of Orthopaedic Surgery, Medical University of Graz, Auenbruggerplatz 5, A-8036, Graz, Austria. birgit.lohberger@medunigraz.at.
authors.forename: Birgit
authors.initials: B
authors.lastname: Lohberger
authors.forename: Nicole
authors.initials: N
authors.lastname: Stuendl
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Wolf
authors.forename: Bernadette
authors.initials: B
authors.lastname: Liegl-Atzwanger
authors.forename: Andreas
authors.initials: A
authors.lastname: Leithner
authors.forename: Beate
authors.initials: B
authors.lastname: Rinner
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000368:Aged; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005354:Fibrosarcoma / Q000201:enzymology* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D059785:Karyotype; D019656:Loss of Heterozygosity; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000201:enzymology*; D050697:Retinal Dehydrogenase / Q000378:metabolism*; D013899:Thoracic Neoplasms / Q000201:enzymology* / Q000473:pathology
chemical_list: D018528:ATP-Binding Cassette Transporters; D007527:Isoenzymes; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase