The effect of bone morphogenetic protein-2 on osteosarcoma metastasis

PLoS One. 2017 Mar 6;12(3):e0173322. doi: 10.1371/journal.pone.0173322. eCollection 2017.

Abstract

Purpose: Bone Morphogenetic Protein-2 (BMP-2) may offer the potential to enhance allograft-host osseous union in limb-salvage surgery following osteosarcoma resection. However, there is concern regarding the effect of locally applied BMP-2 on tumor recurrence and metastasis. The purpose of this project was to evaluate the effect of exogenous BMP-2 on osteosarcoma migration and invasion across a panel of tumor cell lines in vitro and to characterize the effect of BMP-2 on pulmonary osteosarcoma metastasis within a xenograft model.

Experimental design: The effect of BMP-2 on in vitro tumor growth and development was assessed across multiple standard and patient-derived xenograft osteosarcoma cell lines. Tumor migration capacity, invasion, and cell proliferation were characterized. In addition, the effect on metastasis was measured using a xenograft model following tail-vein injection. The effect of exogenous BMP-2 on the development of metastases was measured following both single and multiple BMP-2 administrations.

Results: There was no significant difference in migration capacity, invasion, or cell proliferation between the BMP-2 treated and the untreated osteosarcoma cell lines. There was no significant difference in pulmonary metastases between either the single-dose or multi-dose BMP-2 treated animals and the untreated control animals.

Conclusions: In the model systems tested, the addition of BMP-2 does not increase osteosarcoma proliferation, migration, invasion, or metastasis to the lungs.

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / metabolism*
  • Bone Morphogenetic Protein 2 / pharmacology
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Disease Models, Animal
  • Female
  • Humans
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology*
  • Xenograft Model Antitumor Assays

Substances

  • Bone Morphogenetic Protein 2

Grants and funding

This research was funded in part by Swim Across America, The Matthew Foster Foundation, Barbara Bates Center for The Study of the History of Nursing, and The Barbara Epstein Foundation. We would also like to thank the Pediatric Preclinical Testing Program for the use of their xenograft cell lines and Eugenie S. Kleinerman, MD who kindly provided the SaOS-LM7 cell line. We would also like to acknowledge Daewoong Pharmaceutical Co. Ltd., for graciously providing BMP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.