BMP-2 inhibits the tumorigenicity of cancer stem cells in human osteosarcoma OS99-1 cell line

Cancer Biol Ther. 2011 Mar 1;11(5):457-63. doi: 10.4161/cbt.11.5.14372. Epub 2011 Mar 1.


Previously, based on high ALDH activity, we showed that cancer stem cells (CSCs) could be identified as ALDH(br) cells from an aggressive human osteosarcoma OS99-1 cell line. In this study, we evaluate the impact of BMP-2 on CSCs.Three types of BMP receptors were expressed in freshly sorted ALDH(br) cells. In vitro, growth of the sorted ALDH(br) cells was inhibited by BMP-2. Using RT-PCR analysis, BMP-2 was found to down-regulate the expression of embryonic stem cell markers Oct3/4, Nanog, and Sox-2, and up-regulate the transcription of osteogenic markers Runx-2 and Collagen Type I. In vivo, all animals receiving ALDH(br) cells treated with BMP-2 did not form significant tumors, while untreated ALDH(br) cells developed large tumor masses in NOD/SCID mice. Immunostaining confirmed few Ki-67 positive cells were present in the sections of tumor containing ALDH(br) cells treated with BMP-2. These results suggest that BMP-2 suppresses tumor growth by reducing the gene expression of tumorigenic factors and inducing the differentiation of CSCs in osteosarcoma. BMP-2 or BMP-2-mimetic drugs, if properly delivered to tumor and combined with traditional therapies, may therefore provide a new therapeutic option for treatment of osteosarcoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Dehydrogenase / metabolism
  • Animals
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Cell Line, Tumor
  • Collagen Type I / genetics
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / genetics
  • Humans
  • Ki-67 Antigen / immunology
  • Mice
  • Mice, SCID
  • Nanog Homeobox Protein
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Octamer Transcription Factor-3 / genetics
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology*
  • SOXB1 Transcription Factors / genetics


  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Collagen Type I
  • Core Binding Factor Alpha 1 Subunit
  • Homeodomain Proteins
  • Ki-67 Antigen
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • RUNX2 protein, human
  • SOXB1 Transcription Factors
  • Aldehyde Dehydrogenase