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

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.