Stimulators of mineralization limit the invasive phenotype of human osteosarcoma cells by a mechanism involving impaired invadopodia formation

PLoS One. 2014 Oct 14;9(10):e109938. doi: 10.1371/journal.pone.0109938. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ascorbic Acid / pharmacology*
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology
  • Calcification, Physiologic / drug effects
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Surface Extensions / metabolism*
  • Cell Survival
  • Collagen Type I / metabolism
  • Glycerophosphates / pharmacology*
  • Humans
  • Neoplasm Invasiveness
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology
  • Phenotype
  • Proteolysis

Substances

  • Collagen Type I
  • Glycerophosphates
  • Ascorbic Acid
  • beta-glycerophosphoric acid

Grants and funding

This work was funded by grants 2012/05/N/NZ3/00330 and NN401140639 from the National Science Centre and supported by the EU FP7 Project BIO-IMAGINE:BIO-IMAGing in research INnovation and Education, GA No. 264173 and the Nencki Institute of Experimental Biology. AC is the recipient of Mazovia Scholarship co-financed with the European Union funds by the European Social Fund (8.2.2 Priority). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.