Antiproliferative effects of recombinant human bone morphogenetic protein-2 on human tumor colony-forming units

Anticancer Drugs. 1998 Apr;9(4):327-31. doi: 10.1097/00001813-199804000-00006.

Abstract

Bone morphogenetic protein-2 (BMP-2) is a differentiation factor for normal osteoblasts. BMP-2 is structurally related to transforming growth factor-beta which inhibits cell proliferation and enhances apoptosis. A recent study has shown the presence of BMP-2 receptors on several cancer cell lines. In this study, we attempted to determine if recombinant human BMP-2 (rhBMP-2) can modulate the proliferation of human tumor colony-forming units taken from 113 patients. Tumor cells were cultured in soft agar and continuously exposed to three concentrations of rhBMP-2 (10, 100 and 1000 ng/ml) for 14 days in the capillary cloning system. There were 65 evaluable specimens, including 17 breast cancers, 15 ovarian cancers, 14 non-small cell lung cancers and five prostate cancers. Importantly, rhBMP-2 did not stimulate the tumor cell proliferation. A significant inhibition (50% or less survival of tumor colony-forming units) was seen in 16 of 65 specimens (24.6%) at 1000 ng/ml, including five of 14 non-small cell lung cancers, five of 17 breast tumors and two of 15 ovarian tumors. A concentration-response relationship was observed (p<0.001 by Mantel-extension test). The results of this study encourage further evaluation of the antiproliferative effects of rhBMP-2 against human cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / toxicity*
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Female
  • Humans
  • Male
  • Recombinant Proteins / toxicity
  • Transforming Growth Factor beta*
  • Tumor Cells, Cultured
  • Tumor Stem Cell Assay

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2