Treatment effects of rhBMP-2 on invasiveness of oral carcinoma cell lines

Laryngoscope. 2011 Sep;121(9):1876-80. doi: 10.1002/lary.21914. Epub 2011 Aug 16.

Abstract

Objective: To determine if recombinant human bone morphogenetic protein-2 (rhBMP-2) has biological effects on the invasiveness of human oral squamous cell carcinoma (OSCCA) cell lines.

Study design: Laboratory investigation using six human OSCCA cell lines, with three cell lines having baseline gene expression of BMP-2 and three cell lines without baseline gene expression of BMP-2.

Methods: The invasiveness of each cell line was measured using a matrigel invasion assay with or without stimulation by rhBMP-2. A tumor metastasis quantitative PCR array was used to establish whether observed findings from the invasion assay correlated to changes in gene expression.

Results: There was a significant increase in tumor cell invasion in response to rhBMP-2 in all BMP-2 positive cell lines but no change in the cell lines that did not express the BMP-2 gene. Quantitative PCR revealed that changes in gene expression were distinctly different based on the baseline gene expression of BMP-2 and favored a more metastatic genotype in the BMP-2-positive cells.

Conclusions: Recombinant human BMP-2 has an adverse biological effect on invasiveness of human OSCCA cell lines in vitro. This adverse effect is dependent on the baseline gene expression of BMP-2. Changes in expression of genes involved with tumor metastasis correlated to the invasion assay findings. These data raise concern for the safe application of rhBMP-2 for reconstruction of bone defects in oral cancer patients.

Publication types

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

MeSH terms

  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / genetics
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / genetics
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Real-Time Polymerase Chain Reaction
  • Recombinant Proteins / genetics
  • Recombinant Proteins / pharmacology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / pharmacology*

Substances

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