title: Stimulators of mineralization limit the invasive phenotype of human osteosarcoma cells by a mechanism involving impaired invadopodia formation.
abstract: BACKGROUND
  Osteosarcoma (OS) is a highly aggressive bone cancer affecting children and young adults. Growing evidence connects the invasive potential of OS cells with their ability to form invadopodia (structures specialized in extracellular matrix proteolysis).
  
  
  RESULTS
  In this study, we tested the hypothesis that commonly used in vitro stimulators of mineralization limit the invadopodia formation in OS cells. Here we examined the invasive potential of human osteoblast-like cells (Saos-2) and osteolytic-like (143B) OS cells treated with the stimulators of mineralization (ascorbic acid and B-glycerophosphate) and observed a significant difference in response of the tested cells to the treatment. In contrast to 143B cells, osteoblast-like cells developed a mineralization phenotype that was accompanied by a decreased proliferation rate, prolongation of the cell cycle progression and apoptosis. On the other hand, stimulators of mineralization limited osteolytic-like OS cell invasiveness into collagen matrix. We are the first to evidence the ability of 143B cells to degrade extracellular matrix to be driven by invadopodia. Herein, we show that this ability of osteolytic-like cells in vitro is limited by stimulators of mineralization.
  
  
  CONCLUSIONS
  Our study demonstrates that mineralization competency determines the invasive potential of cancer cells. A better understanding of the molecular mechanisms by which stimulators of mineralization regulate and execute invadopodia formation would reveal novel clinical targets for treating osteosarcoma.
authors.affiliation: Department of Biochemistry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Cmoch
authors.affiliation: Laboratory of Cytometry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Podszywalow-Bartnicka
authors.affiliation: Department of Biological Chemistry, Instituto de Tecnologia Quimica e Biologica, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Palczewska
authors.affiliation: Laboratory of Cytometry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Piwocka
authors.affiliation: Department of Biological Chemistry, Instituto de Tecnologia Quimica e Biologica, Universidade Nova de Lisboa, Oeiras, Portugal.
authors.forename: Patrick
authors.initials: P
authors.lastname: Groves
authors.affiliation: Department of Biochemistry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Slawomir
authors.initials: S
authors.lastname: Pikula
mesh_terms: D001205:Ascorbic Acid / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D002113:Calcification, Physiologic / Q000187:drug effects; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D022081:Cell Surface Extensions / Q000378:metabolism*; D002470:Cell Survival; D024042:Collagen Type I / Q000378:metabolism; D005994:Glycerophosphates / Q000494:pharmacology*; D006801:Humans; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D059748:Proteolysis
chemical_list: D024042:Collagen Type I; D005994:Glycerophosphates; D001205:Ascorbic Acid; C031463:beta-glycerophosphoric acid