Effects of Bone Morphogenetic Proteins on Oral Squamous Carcinoma Cells

Introduction: Human recombinant bone morphogenetic protein-2 (rhBMP-2) is now FDA-approved for maxillofacial applications. Use of BMPs are contraindicated, however, in patients with oral cancer because the biologic effects on carcinoma cells are unknown.

Objective: To determine the in vitro biologic effects of 2 commercially available BMPs on oral carcinoma cells by measuring changes in proliferation, secretion of proangiogenic factors, and secretion of a basement membrane degrading factor.

Methods: RT-PCR was used to detect baseline gene expression of BMPs and BMP-receptors in 3 oral squamous carcinoma cell lines. Proliferation was evaluated by MTT assay at 24 to 72 hrs after exposure to rhBMP-2 or rhBMP-7 (0-100 ng/ml), or after genetic modification using an adenoviral vector with the cDNA for BMP-2 or -7 (moi=0-1000). The supernatant was evaluated via ELISA for expression of VEGF, IL-8, and MMP-9.

Results: BMP-receptors were consistently expressed by all 3 oral cancer cell lines. No significant increase in proliferation was observed after exposure to rhBMP-2 or -7, or when cells were transduced with AdBMP-2 or -7 (p<.05). There was no stimulation of protein expression of the proangiogenic factors VEGF or IL-8 either (p<.05). Upon exposure to higher protein titers (100 ng/ml), some cell lines expressed significantly higher levels of MMP-9.

Conclusions: Treatment of oral carcinoma cells with rhBMP or genetically modifying these cells to express BMPs does not affect proliferation or expression of proangiogenic factors in vitro. Upon exposure to higher levels of protein, there was a significant increase in MMP-9 expression, which may promote basement membrane degradation. Since high doses of protein are used clinically, these data show that further studies are necessary prior to using BMPs in patients undergoing treatment for oral cancer.