title: Impact of sunitinib on human thyroid cancer cells.
abstract: OBJECTIVE
  Thyroid cancer accounts for about 1% of all cancer cases. Multikinase inhibitors like sunitinib (S) have a promising potential in thyroid cancer therapy. Therefore, the principal aim of this study was to investigate the impact of sunitinib on the secretion of cytokines of follicular thyroid cancer cells.
  
  
  METHODS
  The effects of irradiation (R), S, and their combination (R+S) on cytokine secretion by the human thyroid cancer cell lines ML-1 and CGTH W-1 were evaluated after two (d2) and four days (d4) of treatment.
  
  
  RESULTS
  Multi-Analyte Profiling of cytokine release showed a decrease after S treatment (CGTH W-1: IFN-γ, IL-4, IL-8 d2, MIP-1a, MMP-2, TNF-α and TNF-β; ML-1: IFN-γ, IL-4, IL-6, IL-7, IL-8; MIP-1α, MMP-2, MCP-1, TNF-α and TNF-β). R elevated significantly the release of cytokines (exception ML-1: MCP-1, MMP-2; CGTH W-1: IL-4, TNF-β). In contrast, R+S treatment resulted in a reduction of IFN-γ, IL-4, and MMP-2 in both cell lines. IL-6, IL-8 and MCP-1 proteins in the supernatant correlated with the data obtained by quantitative RT-PCR. VEGFD mRNAs were significantly elevated by R+S.
  
  
  CONCLUSIONS
  A target-based therapy with R+S changed VEGFD, IL-6 and IL-8 in follicular thyroid cancer cells. These in vitro-experiments suggest IL-6, IL-8, VEGFD and TNF-α as interesting biomarkers to be investigated in vivo. Different reactions of the cell lines under equal treatment might be due to their different origin and characteristics.
authors.affiliation: Department of Nuclear Medicine, University of Regensburg, Regensburg, Germany.
authors.forename: Jirka
authors.initials: J
authors.lastname: Grosse
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Warnke
authors.forename: Fabian
authors.initials: F
authors.lastname: Pohl
authors.forename: Nils E
authors.initials: NE
authors.lastname: Magnusson
authors.forename: Markus
authors.initials: M
authors.lastname: Wehland
authors.forename: Manfred
authors.initials: M
authors.lastname: Infanger
authors.forename: Christoph
authors.initials: C
authors.lastname: Eilles
authors.forename: Daniela
authors.initials: D
authors.lastname: Grimm
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D011839:Radiation, Ionizing; D000077210:Sunitinib; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects; D042643:Vascular Endothelial Growth Factor D / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D007211:Indoles; D015850:Interleukin-6; D016209:Interleukin-8; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C579459:VEGFD protein, human; D042643:Vascular Endothelial Growth Factor D; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077210:Sunitinib