title: Osteosarcoma cells differentiate into phenotypes from all three dermal layers.
abstract: BACKGROUND
  Osteosarcomas are the most common solid malignant bone tumors, but little is known of their origin. The embryonal rest hypothesis views cancer cells as arising from committed progenitor stem cells in each tissue. Adult tissue contains primitive stem cells that retain the ability to differentiate across dermal lines, raising the possibility that the stem cell of origin of cancers may be from a more primitive stem cell than a progenitor.
  
  
  OBJECTIVE
  Can osteosarcoma cells, when cultured under conditions used for multipotent stem cells, be induced to differentiate into multiple phenotypes, including those of the three different dermal lineages: mesodermal, ectodermal, and endodermal?
  
  
  METHODS
  One rat and one human osteosarcoma cell line were cultured and treated with concentrations of 0, 10(-10), 10(-9), 10(-8), 10(-7), and 10(-6) mol/L dexamethasone for 5 weeks. Seventeen phenotypes were assayed either by tissue-specific histochemical stains or antibodies to tissue-specific proteins. Each phenotype was tested across all dexamethasone concentrations for each cell line and each phenotype was tested in three separate experiments with induction by dexamethasone
  
  
  RESULTS
  Rat osteosarcoma (ROS) 17/2.8 and human osteosarcoma cell line U-2 show the appearance of cells that have markers for (1) mesodermal phenotypes such as bone, cartilage, skeletal muscle, and endothelial cells, (2) ectodermal phenotypes such as astrocytes, oligodendrocytes, neurons, and keratinocytes, and (3) an endodermal phenotype, hepatocytes. This indicates osteosarcomas are composed, at least in part, of primitive stem cells capable of differentiating into tissues from all three dermal lineages.
  
  
  CONCLUSIONS
  If osteosarcomas arise from primitive stem cells, then treatment of osteosarcomas with exogenous differentiation agents may cause the stem cells to differentiate, thus halting their proliferation and stopping tumor growth.
authors.affiliation: Department of Orthopedic Surgery, Macy Pavillion, New York Medical College, Valhalla, NY, 10595, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Russinoff
authors.forename: Sara
authors.initials: S
authors.lastname: Miran
authors.forename: Ashok L
authors.initials: AL
authors.lastname: Gowda
authors.forename: Paul A
authors.initials: PA
authors.lastname: Lucas
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D019070:Cell Lineage; D054338:Cell Transdifferentiation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004475:Ectoderm / Q000473:pathology; D004707:Endoderm / Q000473:pathology; D006801:Humans; D008648:Mesoderm / Q000473:pathology; D039902:Multipotent Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D051381:Rats; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D003907:Dexamethasone