title: Tumourigenicity and radiation resistance of mesenchymal stem cells.
abstract: BACKGROUND
  Cancer stem cells are believed to be more radiation resistant than differentiated tumour cells of the same origin. It is not known, however, whether normal nontransformed adult stem cells share the same radioresistance as their cancerous counterpart.
  
  
  METHODS
  Nontumourigenic (TERT4) and tumourigenic (TRET20) cell lines, from an immortalised mesenchymal stem cell line, were grown in culture prior to irradiation and gene expression analysis. Radiation resistance was measured using a clonogenic assay. Differences in gene expression between the two cell lines, both under nontreated and irradiated conditions, were assessed with microarrays (Affymetrix Human Exon 1.0 ST array). The cellular functions affected by the altered gene expressions were assessed through gene pathway mapping (Ingenuity Pathway Analysis).
  
  
  RESULTS
  Based on the clonogenic assay the nontumourigenic cell line was found to be more sensitive to radiation than the tumourigenic cell line. Using the exon chips, 297 genes were found altered between untreated samples of the cell lines whereas only 16 genes responded to radiation treatment. Among the genes with altered expression between the untreated samples were PLAU, PLAUR, TIMP3, MMP1 and LOX. The pathway analysis based on the alteration between the untreated samples indicated cancer and connective tissue disorders.
  
  
  CONCLUSIONS
  This study has shown possible common genetic events linking tumourigenicity and radiation response. The PLAU and PLAUR genes are involved in apoptosis evasion while the genes TIMP3, MMP1 and LOX are involved in regulation of the surrounding matrix. The first group may contribute to the difference in radiation resistance observed and the latter could be a major contributor to the tumourigenic capabilities by degrading the intercellular matrix. These results also indicate that cancer stem cells are more radiation resistant than stem cells of the same origin.
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Nørrebrogade 44, Aarhus C, Denmark. filippo@oncology.dk
authors.forename: Filippo P
authors.initials: FP
authors.lastname: D'Andrea
authors.forename: Michael R
authors.initials: MR
authors.lastname: Horsman
authors.forename: Moustapha
authors.initials: M
authors.lastname: Kassem
authors.forename: Jens
authors.initials: J
authors.lastname: Overgaard
authors.forename: Akmal
authors.initials: A
authors.lastname: Safwat
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D049109:Cell Proliferation / Q000528:radiation effects; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000528:radiation effects*; D009369:Neoplasms / Q000235:genetics / Q000473:pathology* / Q000532:radiotherapy; D014411:Neoplastic Stem Cells / Q000473:pathology* / Q000528:radiation effects*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger