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

Authors

  • Natalia A. Kokorina MD,

    1. Department of Otolaryngology—Head & Neck Surgery, Washington University School of Medicine, St. Louis, Missouri, U.S.A.
    Current affiliation:
    1. Department of Medicine at the University of Medicine and Dentistry of New Jersey (UMDNJ)
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  • Stanislav O. Zakharkin PhD,

    1. Department of Technology and Innovation, Solae, St. Louis, Missouri, U.S.A.
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  • Paul H. Krebsbach DDS, PhD,

    1. Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan, U.S.A.
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  • Brian Nussenbaum MD

    Corresponding author
    1. Department of Otolaryngology—Head & Neck Surgery, Washington University School of Medicine, St. Louis, Missouri, U.S.A.
    • Department of Otolaryngology—Head & Neck Surgery, Washington University School of Medicine, 660 South Euclid Ave., Campus Box 8115, St. Louis, MO 63110
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  • Presented at the 114th Annual Meeting for the Triological Society, Chicago, Illinois, April 29, 2011.

  • The authors have no financial disclosures for this article.

  • §

    The authors have no conflicts of interest to disclose.

  • Funding Sources: NIDCR/NIH Grant DE017137-01A1 and internal research funds from the Department of Otolaryngology—Head & Neck Surgery at Washington University School of Medicine.

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.

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