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.


METHODS
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.
Department of Otolaryngology-Head & Neck Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
Natalia A
NA
Kokorina
Stanislav O
SO
Zakharkin
Paul H
PH
Krebsbach
Brian
B
Nussenbaum
D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology*
D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2