title: Ras/Raf/MEK/ERK pathway is associated with lung metastasis of osteosarcoma in an orthotopic mouse model.
abstract: OBJECTIVE
  To identify a marker of osteosarcoma metastasis and to inhibit the marker against the invasive ability of an osteosarcoma cell line (143B).
  
  
  METHODS
  Type I insulin-like growth factor receptor (IGF-1R) and its downstream signalling factors were measured in samples from our orthotopic 143B mouse model by immunohistochemistry. A Matrigel assay was used to assess cell invasion ability under interference.
  
  
  RESULTS
  All 15 mice had tumour mass at the left tibia. Total IGF-1R, MEK, Akt, p38 and phosphorylated MEK (p-MEK), but not p-Akt and p-p38, were positive in both local tumours and lung secondaries. Leiomyosarcoma controls expressed p-Akt and p-MEK, but not p-p38. The 143B cells treated with U0126, a MEK/ERK inhibitor, had significantly lower in vitro invasion ability compared with controls.
  
  
  CONCLUSIONS
  The IGF-1R-MEK signalling pathway, particularly Ras/Raf/MEK/ERK, may play an important role in osteosarcoma lung metastasis, and the targeting MEK/ERK by its specific inhibitor may have a potential use in the effective treatment of osteosarcoma.
authors.affiliation: Prince of Wales Clinical School, University of New South Wales, Randwick, NSW 2031, Australia. y.yu@unsw.edu.au
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.forename: Frederick
authors.initials: F
authors.lastname: Luk
authors.forename: Jia-Lin
authors.initials: JL
authors.lastname: Yang
authors.forename: William R
authors.initials: WR
authors.lastname: Walsh
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism / Q000556:secondary*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D048490:raf Kinases / Q000378:metabolism*
chemical_list: D051057:Proto-Oncogene Proteins c-akt; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D016283:Proto-Oncogene Proteins p21(ras)